fluid and electrolyte balance, anaemia and blood transfusion

PerioPerative

Fluid and electrolyte balance, anaemia and blood transfusionDavid o’Hara

Patricia richardson

Abstractan understanding of the basic physiology of fluid and electrolyte balance

and the impact of surgery and anaesthesia on homeostatic mechanisms

is essential to safe patient management in the perioperative period.

Successful fluid management also requires familiarity with both the com-

position and pharmacology of commonly available products for fluid

replacement therapy. a greater awareness of the hazards of blood and

blood components has led to significant changes in practice over the

last 20 years; traditional transfusion triggers have been challenged and

more restrictive strategies adopted.

Keywords blood component transfusion; blood transfusion autologous;

fluid therapy; water–electrolyte balance

An understanding of the basic physiology of fluid and electrolyte balance and the impact of surgery and anaesthesia on homeo-static mechanisms is essential to safe patient management in the perioperative period. The report An Acute Problem, published in 2005 by the National Confidential Enquiry into Patient Out-come and Death (NCEPOD), identified poor fluid management as contributing to preventable morbidity and mortality, echoing findings of previous reports.

Fluid compartments

Body water is considered to exist in physiologically discrete col-lections known as compartments. The major division is into intracellular fluid (ICF) and extracellular fluid (ECF), based on which side of the cell membrane water lies (Table 1).

A 70 kg adult male body has 42 litres of water (60% of body weight), of which 28 l is intracellular and 14 l extracellular. Females, who typically have more body fat than males, have less water per unit of body weight. Extracellular fluid is further subdivided into: • intravascular fluid (plasma), which with blood cells accounts

for a total blood volume of 4.5 litres (6% of body weight). • interstitial fluid which lies in tissues outside the vascular

system (9.5 litres; 14% of body weight).

David O’Hara FRCA is a Specialist Registrar in Anaesthesia at the

Broomfield Hospital, Chelmsford, Essex, UK. Conflicts of interest: none

declared.

Patricia Richardson FRCA is a Consultant Anaesthetist at the Broomfield

Hospital, Chelmsford, Essex, UK. Conflicts of interest: none declared.

SUrGerY 26:9 383

• transcellular fluid (i.e. synovial fluid, cerebrospinal fluid, vit-reous and aqueous humor).

Fluid movement

Two forces govern the movement and distribution of water be-tween the intracellular and interstitial spaces: • osmotic gradients (created by differences in non-diffusible

solute concentrations) • hydrostatic pressure gradients, governed by the relationship

between compartment volume (e.g. circulating volume) and the tension of the walls of the compartment (e.g. venous tone).There is a negligible hydrostatic pressure difference between

the ICF and ECF, and so fluid movement is regulated principally by the osmotic gradients. The cell membrane lipid bilayer, sep-arating the ICF and ECF is freely permeable to water, but not solutes. Potassium and sodium are the predominant cations in the ICF and ECF respectively, and can pass only through spe-cific voltage or ligand-gated ion channels. The inequality in ion concentrations create a transmembrane potential, which is main-tained by the Na-K ATPase pump.

Changes in the ICF and ECF osmolality results in the move-ment of water from the lower to higher osmalarity compartment.

In contrast, capillary endothelium is non-selective and freely permeable to both water and ions, thus plasma and interstitial fluid have similar compositions.

The movement of water between the intravascular and intersti-tial compartments is governed by hydrostatic and osmotic pressures, the latter termed colloid oncotic pressure because the vascular endo-thelium is impermeable to large molecules (colloids). Water flux between these compartments is governed by Starling’s equation:

Fluid flux = (Pc − Pi) − (πc − πi) σ

where Pc is capillary hydrostatic pressure, Pi is interstitial hydrostatic pressure, πc is capillary oncotic pressure, πi is interstitial oncotic pressure and σ is the reflectance coefficient - a constant reflecting membrane permeability. In hypoprotinaemic states (e.g. hypoal-buminaemia) the capillary oncotic pressure is reduced, leading to water movement into the interstitium and oedema formation.

Control of body water

In health, total body water is maintained at a fairly constant level. In adults daily water intake (dietary, 2200 ml; metabolic, 300 ml)

Distribution of total body water among body fluid compartments (70-kg male)

% of body

weight

% of total

body water

Volume

(litres)

Extracellular fluid 20 33 14

Plasma 6 9 4.5

interstitial fluid 14 24 9.5

Intracellular fluid 40 66 28

Table 1

© 2008 elsevier Ltd. all rights reserved.

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is balanced by water lost in urine (1500 ml) and faeces (100 ml), and insensible losses from skin and lungs (900 ml).

This balance is controlled by the thirst - antidiuretic hormone (ADH) mechanism, with thirst affecting input and anti-diuretic hormone (ADH) regulating output.Thirst is a conscious sensation to drink, originating in the hypothalamus, and stimulated by: • hypertononicity, detected by osmoreceptors in the

hypothalamus • hypovolaemia, detected by volume receptors in the right

atrium and great veins • hypotension, detected by baroreceptors in the carotid sinus

and aortic arch • angiotensin II.

ADH (vasopressin) is produced in the hypothalamus and released into the circulation from the posterior pituitary gland in response to several stimuli: • increased plasma tonicity • hypovolaemia • hypotension • angiotensin II • stress (including the stress response to surgery) • drugs (such as opiates).ADH acts on the principal cells of the collecting duct to increase reabsorption of water via specific ADH-sensitive (aquaporin) channels.

Electrolyte balance and clinical implications

SodiumSodium is the principal intracellular cation, and is the key regula-tor of water flux. Hyponatraemia (Table 2) in surgical patients is most commonly caused by inappropriate administration of low sodium or sodium free solutions, particularly postoperatively, when increased ADH secretion causes water retention. Acute hyponatraemia – a medical emergency - is defined as a plasma sodium concentration <120 mmol l−1 developing over less than 48 hours. Symptoms are those of cerebral oedema; progressing from nausea and headache to confusion, seizures and finally brainstem herniation and death. Prompt correction aiming to

Causes of hyponatraemia

Hypovolaemia Normovolaemia Hypervolaemia

Diarrhoea SiaDH Congestive cardiac

failure

vomiting Hypothyroidism Nephrotic syndrome

third-space losses Stress Cirrhosis

Diuretic abuse renal failure

renal tubular

Hypoadrenalism

Salt-losing

nephropathy

SiaDH, syndrome of inappropriate antidiuretic hormone secretion.

Table 2

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increase the plasma sodium concentration by 2 mmol l−1 hr−1 until symptoms resolve can avoid such serious consequences.

Hypernatraemia (Table 3) is less common and is associ-ated with an increased plasma osmolality and thirst. Symptoms include nausea, vomiting, confusion, drowsiness, seizures and coma. Treatment should aim to restore the circulating volume to normal with isotonic fluids over 48–72 hours.

PotassiumPotassium is predominantly an intracellular cation. Homeostasis is achieved by matching urinary losses to intake by secretion of potassium in the distal convoluted tubule. Alterations in the ECF potassium concentration reflect disturbance of total body potassium content (intake vs loss) or changes in the ratio of extra-cellular to intracellular potassium.

Hypokalaemia (Table 4) leads to anorexia, nausea, muscle weakness, paralytic ileus and cardiac conduction abnormalities. Treatment requires potassium supplementation and treatment of the underlying cause.

Hyperkalaemia (Table 5), which may cause life threatening cardiac arrhythmias, requires immediate treatment. Intravenous calcium gluconate, glucose and insulin, sodium bicarbonate; rec-tal calcium resonium or haemodialysis may be used, depending on the clinical situation and urgency.

ChlorideChloride, the main anion in ECF, is important in maintaining normal acid–base status, renal tubular function and formation of gastric acid. The chloride concentration passively mirrors that of sodium and is inversely related to plasma bicarbonate. In the proximal renal tubule, chloride is excreted with ammonium ions to eliminate hydrogen ions in exchange for sodium and thus acid-ify urine. Hypochloraemia can occur with loss of gastric, pancre-atic, bile and intestinal secretions. Excessive infusion of chloride containing fluids (e.g. saline, gelatins), will lead to hyperchlorae-mia. This has important implications in acid–base regulation and

Causes of hypernatraemia

Cause Examples

Pure water depletion

extrarenal loss Failure of water intake (postoperative,

coma, elderly)

Mucocutaneous loss

Fever, hyperventilation, thyrotoxicosis

renal loss Diabetes insipidus (nephrogenic,

cranial)

Chronic renal failure

Hypotonic fluid loss

extrarenal loss Gastrointestinal (vomiting, diarrhoea)

Skin (excessive sweating)

renal loss osmotic diuresis (glucose, alcohol,

mannitol)

Salt gain iatrogenic (NaHCo3, hypertonic saline)

Salt ingestion

Table 3

4 © 2008 elsevier Ltd. all rights reserved.

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will lead to a hyperchloraemic metabolic acidosis. Infusion of a large volume of normal saline can precipitate a metabolic acido-sis because renal sodium excretion occurs in preference chloride and hydrogen ion excretion (Table 6).

Anaesthesia, surgery and fluid balance

The impact of the physiological response to surgical stress, along with the various fluid shifts that may occur mean that accurate assessment of hydration is paramount. Many patients are dehy-drated before surgery due to prolonged fasting, bowel prepara-tion or diuretics. Perioperative losses are often underestimated, with fluid loss from drains and sequestration of fluid in tissues and the gastrointestinal tract (third space losses) persisting into the postoperative period.

The stress response to surgery has two main components - neuroendocrine and cytokine. The neuroendocrine response is stimulated initially by afferent nociceptive stimuli reaching the central nervous system and may be blunted by regional anaes-thesia and opioids. It is characterized by an increase in ADH, adrenocorticotropic hormone (ACTH), growth hormone (GH), cortisol and aldosterone secretion, and activation of the sympa-thetic nervous system and renin-angiotensin system. This results in sodium and water retention, the magnitude of which is modu-lated by factors such as the effects of anaesthetic agents on renal blood flow and glomerular filtration rate, hypotension, and renal

Causes of hypokalaemia

Cause Examples

abnormal gastrointestinal loss vomiting

Diarrhoea

villous adenoma

increased renal loss Drugs (diuretics), metabolic

acidosis, magnesium depletion

eCF–iCF shift Drugs (insulin, b-agonists),

metabolic alkalosis

eCt, extracellular fluid; iCF, intracellular fluid.

Table 4

Causes of hyperkalaemia

Cause Examples

Decreased renal

clearance

renal failure, drugs (b-blockers, aCe inhibitors)

Metabolic acidosis

adrenocortical failure

iCF–eCF shift tissue damage (burns, crush injury, haemolysis

Metabolic acidosis

aCe, angiotensin converting enzyme; eCt, extracellular fluid; iCF, intracellular fluid.

Table 5

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vasoconstriction secondary to catecholamines. ADH concentra-tions may increase by 50–100 fold, and do not return to normal for 3–5 days, accounting for postoperative period of oliguria.

The cytokine response is stimulated by local tissue damage at the site of surgery in proportion to the extent of damage and is unaffected by neural blockade. It leads to increased capillary membrane permeability and third space fluid losses.

Assessment of hydration

Accurate clinical assessment of intravascular volume is often difficult and laboratory investigations are invariably required to guide perioperative fluid therapy. Thirst, skin turgor, hydration of mucous membranes, core-periphery temperature gradient, res-piratory rate, pulse rate and volume, orthostatic hypotension and urine output are valuable signs of hydration. Unfortunately there are many confounding factors that may influence these, such as drugs, surgical stress, age and underlying disease. Laboratory signs of dehydration include: • hypernatraemia • rising haematocrit • progressive metabolic acidosis • rising lactate • increased serum urea to creatinine ratio • urinary sodium <20 mmol/litre • Urine osmolality approaching 1200 mosmol/kg.

In more complex cases central venous pressure (CVP) may be required. Observation of the haemodynamic and clinical response to the rapid intravenous infusion of a small volume of fluid (e.g. 250–500 ml over 20–30 minutes) permit assess-ment of the compliance of the circulation and intravascular vol-ume status. Such fluid challenges may be repeated successively if there is no, or a transient change in CVP. A sustained rise in CVP of 3 cmH2O is considered evidence of adequate fluid administration.

A practical approach to clinical fluid prescribing

Intravenous fluid administration has two goals: meeting daily maintenance requirements, and correct existing and ongoing water and electrolyte losses. In the adult, the daily maintenance requirements (water 35 ml kg−1, sodium 2 mmol kg−1, potas-sium 1 mmol kg−1) can be provided by 1000 ml normal saline and 1500 ml 5% glucose with the addition of potassium 20 mmol l−1 to each litre of fluid. Correction of ongoing extracellular fluid losses, which have a composition similar to that of plasma, is best achieved with lactated Ringer’s (Hartmann’s) solution. It is important that the volume of intravenous drugs and nutrition is taken into account.

Osmolarity, osmolality and tonicity

The terms osmolarity, osmolality and tonicity are often and incorrectly used interchangeably. Osmolarity (expressed in mil-liosmoles per litre of solution) and osmolality (expressed in mil-liosmoles per kilogram of solvent) describes the number of all the solutes that contribute to a solution’s osmotic pressure. Plasma osmolarity, which is normally 280–300 mOsm l−1, can be esti-mated using the formula:


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Electrolyte composition, pH and osmolality of body compartments, secretions and commonly used intravenous fluids

Fluid Na+ K+ Ca2+ Mg2+ Cl– HCO3−1 pH Osmolality Plasma volume

T½ (min)

Body compartment

Plasma 142 4 2.5 1 100 25 7.4 280

interstitial fluid 145 4 2.4 0.9 118 27 7.4 280

intracellular fluid 12 155 0 15 8 10 7.2 280

Secretions

Saliva 50–70 15–20 – – 10–15 30–50 6–7

Gastric juice 150 5–10 – – 100–160 10–20 1–3.5

Bile 180–220 6–8 – – 60–70 60–70 7–8

Pancreatic juice 160 4 – – 30–60 80–120 8–8.3

Small bowel 140 4 – – 100 25 7.8–8

Crystalloids

Normal saline (0.9% NaCl) 154 – – – 154 – 5 300 80

Hartmann`s solution 131 5 2 – 111 6.5 275 68

Dextrose 4% saline 0.19% 31 – – – 31 – 4.5 286

Dextrose 5% – – – – – – 4.2 278 19

Bicarbonate 8.4% 1000 – – – – 1000 8 2000 –

Colloids

Gelofusine 154 0.4 0.4 0.4 120–125 – 7.4 274 180

Hydroxyethyl starch (450/0.7) 154 – – – 154 – 5.5 300–310 75

Hydroxyethyl starch (130/0.4) 154 – – – 154 – 5.0 308 700

Dextran 40 154 – – – 154 – 3.5–7.0 280–324 180

Dextran 70 154 – – – 154 – 5.0 280–324 1500

HaS 4.5% 100–160 <2.25 – – 100–160 – 5.5 200–310 1000

HaS, human albumin solution; HCo3–, bicarbonate. reproduced from Mackenzie i. Fluid and electrolyte balance. Surgery 2005; 23: 453–60.

Table 6

Osmolarity = (1.86×[Na+])+[glucose]+[urea]+9 mOsm l−1

Fluids such as normal saline and 5% glucose (300 mOsm l−1) are iso osmolar, whereas 10% glucose and 1.8% saline (600 mOsm l−1) are hyperosmolar. In contrast, tonicity describes only the number of solutes that cannot cross cell membranes. Thus normal saline is described as being isotonic whereas 4% glucose in 0.18% saline (300 mOsm l−1) is hypotonic because membranes are permeable to glucose.

Intravenous fluids

In most territories fluids for intravenous infusion are classed as ‘prescription only medicines’ and should, therefore, be regarded as ‘drugs’ – each having pharmacokinetic and pharmacodynamic properties, interactions and side-effect profiles. For this reasons fluids must be prescribed with the same care and attention as any other drug.1,2

CrystalloidsCrystalloids are simple electrolyte solutions, whose distributon within the body is governed by their osmolarity and tonicity. Flu-ids such as saline and Hartmann’s solution, which have a sodium concentration similar to that of ECF, remain within the ECF. If used to replace blood loss, 3 to 4 times the volume lost must be

SUrGerY 26:9 38

administered as only 25–30% will remain in the intravascular compartment.

Following the administration of hypotonic solutions, such as 5% glucose, the membrane permeable solute (i.e. glucose) is readily taken up by cells. The net effect is that of administering pure water, which distributed throughout each compartment in proportion to its contribution to total body water.

Synthetic colloidsDerived from the Greek word for glue, the term colloid refers to the dispersion – as apposed to solution - of one substance within another. Macromolecules suspended in water are known as hydrocolloids. Synthetic colloids for clinical use are iso osmolar crystalloid or glucose solutions containing a suspension of semi-synthetic polypeptides or polysaccharides with molecular weight >30,000 kDa, which exert an osmotic force across capillary walls. Because they tend to remain in the circulation for longer than crys-talloid solutions, blood replacement can be achieved with smaller volumes of colloid and without the infection transmission risk of blood products. Colloids are more costly than crystalloids and have a small but significant risk of adverse allergic reactions.

GelatinsModified gelatins (e.g. Gelofusine, Haemaccel, Volplex), which are derived from animal skin and bone, are the most commonly


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used colloids in the UK. Gelatin molecules have a wide range of sizes and each solution is described as the weight-average molec-ular weight (Mw) - typically 30 kDa. Most of the administered dose is excreted unchanged in the urine, 10% excreted in faeces and 3% metabolised. There is no long-term retention.

StarchesStarches are produced from amylopectin, which has been stabi-lised by hydroxylation to prevent rapid hydrolysis by amylase. Solutions are fractionated to yield the desired ranges of molec-ular weights (e.g. hydroxyethyl starch Mw 200 kDa). Starches are thought to reduce capillary leak by ‘plugging’ holes in the endothelial basement membrane, but their use in sepsis has been shown to be an independent risk factor for renal failure. Starches have a longer plasma half-life than gelatins and this has lead to their popularity. However, there is no evidence base to suggest any outcome benefit over gelatins.

DextransDextrans are highly branched polysaccharide molecules synthe-sized from sucrose by the bacterium Leuconostoc mesenteroides. The formulations currently available are Dextran 40 (Mw 40 kDa) and Dextran 70 (Mw 70 kDa). The rate and extent of renal elimi-nation is a function of molecular weight, with half of Dextran 40 being excreted within a few hours of administration, whilst Dextran 70 has a duration of action of 6–8 hours. Dextrans are used to improve microcirculatory flow by reducing erythrocyte aggregation and leucocyte plugging, but interfere with platelet aggregation, by reducing concentrations of von Willebrand fac-tor and enhance fibrinolysis. Dextrans cause severe anaphylactic reactions more frequently than gelatins or starches.

Natural colloidsHuman albumin solution (HAS): albumin makes up 60% of plasma protein and contributes to 80% of plasma colloid osmotic pressure. It has additional functions as a carrier in the blood. Human albumin solution (HAS, 66 kDa) is harvested and pooled from blood donors for use either as a dilute (4.5–5%) or con-centrated, or salt-poor (20–25%) solution. HAS has an excellent safety record and pasteurisation has been shown to be highly effective at inactivating viruses such as hepatitis A, B and C and human immunodeficiency virus (HIV). Concerns about varient Creutzfeld-Jacob disease (vCJD) transmission has led to HAS used in the UK being sourced from USA.

A meta-analysis, published in 2004 by the Cochrane Review Group, controversially claimed that, when used for resuscitation and volume expansion in critically ill patients, HAS was associ-ated with an excess mortality of 6%. The reputation of HAS was partially restored following subsequent publication of the saline versus albumin fluid evaluation (SAFE) study, which showed clinically equivalent outcomes in intensive care patients.

Despite the high cost of HAS, it still has a role in the restoration of plasma volume following the acute phase of critically illness in situations of sodium and water overload. Concentrated solutions may promote diuresis in cirrhotic, hypoalbuminaemic patients.

Controversy still exists as to which is the most appropriate fluid for use in the perioperative period. Systematic reviews show no significant differences in pulmonary oedema, mortality or length of stay between colloid or crystalloid resuscitation.

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Blood transfusion

An awareness of the potentially devastating effects of disease transmission resulting from blood product use has brought about significant changes in transfusion medicine in the last 20 years. The development of clotting factor concentrates pooled from up to 30,000 donors initially liberated haemophiliacs from frequent periods of hospitalisation. Sadly, this led to widespread exposure of patients to hepatitis B (HVB) and C (HVC), and subsequently HIV. By the time viral inactivation processes were introduced in 1985 it was estimated that in the UK 4,800 haemophiliacs had been infected with HVC and of these 1,200 with HIV.

Four cases of vCJD have been reported in the UK following blood transfusion; the first case being identified in December 2003. In all cases the donor developed symptoms of the disease 18 months or later after donating blood. As a response to this rare but devastating risk, blood in the UK is now supplied ‘leu-cocyte deplete’ to minimise prion transmission. The risk of cyto-megalovirus (CMV) transmission is similarly minimised by this precaution. Leucocyte depleted blood contains <5 × 106 leuco-cytes per unit of red cells.

Every unit of blood donated in the UK is tested for hepatitis B surface antigen, hepatitis C antibody and RNA, HIV antibody, HTLV antibody, and syphilis antibody.

Perioperative anaemia and transfusion triggersFor many years it was thought that patients should be trans-fused to achieve a haemoglobin concentration of 10 g dl−1 and a haematocrit of 30%. The publication in 1999 of the Transfusion Requirements in Critical Care (TRICC) study showed that a hae-moglobin target of 7–9 g dl−1 in critically ill patients was associ-ated with no worse 30 day mortality and morbidity than a more liberal target of 10–12 g dl−1. Subgroup analysis of patients with known coronary artery disease echoed this finding of reduced complications and indeed the liberal transfusion strategy group had a higher incidence of pulmonary oedema. Only those with severe ischaemic heart disease showed a non-statistically signifi-cant difference in absolute survival rates.

The indications for blood transfusion detailed in the 2002 Department of Health (UK) circular (HSC2002/09) are sum-marised in Table 7. The decision to transfuse should be made by senior clinicians aware of the risks and benefits. The justifica-tion for transfusion must be discussed with the patient whenever possible and documented. HSC2002/09 sets out a target haemo-globin concentration of 7 g dl−1 for patients undergoing surgery. This may be most appropriately achieved without transfusion with dietary supplementation such as vitamin B12, folate and iron. It should be noted that such therapies only reduce the rate of transfusion where haematinic deficiency is the cause of the anaemia. There is no standard transfusion trigger that will pro-vide an optimal risk-benefit profile in all preoperative patients and the justification for transfusion must take into account the urgency of surgery, cause anaemia and medical condition of the patient.

Donor red blood cellsDonor blood is immediately cooled to and stored at 4°C which produces erythrocyte changes or ‘storage lesions’. These include an increase in extracellular potassium concentration (20 mmol l−1


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Indications for blood transfusion

Indication Details

acute blood loss Blood volume loss (%) Fluid role of blood transfusion

15–30 Crystalloid/colloid Unlikely

30–40 Crystalloid/colloid Probable

> 40 Crystalloid/colloid required

the aim is to maintain circulating blood volume and Hb concentration above 7 g/dl in fit patients,

and above 9 g/dl in elderly patients and those with cardiovascular disease

Perioperative transfusion Most patients should not require transfusion. Use Hb to guide blood transfusion

Healthy patient: aim for Hb 7 g/dl

Cardiovascular disease or significant risk factors (elderly, hypertension, diabetes mellitus, peripheral

vascular disease): aim for Hb 9 g/dl

Critical care transfuse to Hb > 7 g/dl

Post-chemotherapy No evidence base to guide transfusion trigger

radiotherapy transfuse to maintain Hb above 10 g/dl

Chronic anaemia transfuse to lowest Hb concentration to alleviate symptoms

other transfusion may also be indicated in the management of inherited and acquired red blood cell

disorders and in cases of marrow failure. Seek specialist haematological advice

Hb, haemoblobin concentration.

Table 7

after 3 weeks of storage) and decreased triphosphate and 2,3 diphosphoglycerate levels, the latter hindering oxygen binding. After 3 weeks stored blood has a pH of 6.9 and bicarbonate con-centration of 10 mmol l−1. Erythrocyte membranes become rigid and fragile resulting in enhanced haemolysis. Clotting factor activ-ity in whole blood decreases rapidly and is significantly reduced after 7 days of storage. For this reason plasma is separated from erythrocytes and administered separately as fresh frozen plasma (FFP). Erythrocyte have a shelf life of 35 days and are usually supplied as concentrated cells with a haematocrit of 55–75%. In the UK erythrocytes are usually suspended in saline, adenine, glucose and mannitol (SAG-M); the plasma having been removed and used for other blood components. The use of SAG-Mannitol makes the resulting suspension less viscous. Red cell blood is leu-codepleted to minimise transmission of infections (CMV, vCJD). Gamma irradiation is performed to reduce lymphocyte transmis-sion and is required solely for immunological reasons in patients with inherited or acquired immunodeficiency states.

Complications of blood transfusion

Despite major advances in blood transfusion safety, hazards associated with blood transfusion do exist, and prompt recogni-tion and treatment is essential (Table 8).

Transfusion-related acute lung injury (TRALI)TRALI remains a rare complication of the transfusion of any blood component that is believed to be significantly under reported. The clinical picture is one of a severe acute pulmonary reaction clinically indistinguishable from acute respiratory distress syn-drome (ARDS). However, improvement usually occurs within 48–96 hours provided timely supportive treatment is initiated. The mortality rate is 5% in contrast to 30–60% seen in ARDS.

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In cumulative analyses of Serious Hazards of Transfusion (SHOT) data (see below) TRALI remains a leading cause of transfusion-related mortality and morbidity, second only to ABO incompatibility. It is difficult to accurately quote an incidence. One US hospital with a particular interest in TRALI quotes 0.02% (1 in 5000 units of blood), whereas the 2006 UK SHOT report quotes an incidence of 0.004% (1 in 200,000 units).

TRALI occurs 5–6 times more frequently following the admin-istration of platelets and FFP than erythrocytes and in 90% of cases donor leucocyte antibodies, reacting with patient leuco-cytes can be detected. The resultant complement-mediated leu-cocyte activation leads to pulmonary endothelial damage. Blood donors subsequently shown to have human leucocyte antigen (HLA) or granulocyte-specific antibodies should not be used again as donors. Multiparous women are more likely to fall into this group. All FFP (a pooled product) in the UK now comes from male donors.

Massive blood transfusionMassive blood transfusion is defined as the complete replace-ment of the entire blood volume within a 24-hour period. This is associated with additional risks to those related to smaller trans-fusions, which result from metabolic alterations in the blood as a result of cooling and storage. The adverse consequences are shown in Table 9.

Serious Hazards of TransfusionThe Serious Hazards of Transfusion (SHOT) scheme is a UK based organisation established in 1996 with the aim of collect-ing and investigating reports of major adverse events following blood transfusion and focuses on particular predefined catego-ries. Although reporting remains voluntary, all UK hospitals are actively encouraged to report and engage in ‘haemovigilance’.


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Complications of blood transfusion

Complication Details

Febrile non-haemolytic

transfusion reactions

Common, especially in parous women and after previous transfusions

Mediated by donor leucocytes

Benign but must be differentiated from life-threatening haemolytic reactions

Flushing, fever, tachycardia, rigors

treat by slowing transfusion rate and with paracetamol

abandon transfusion if >1.5°C temperature rise and consult laboratory

acute haemolytic


intravascular haemolysis owing to aBo compatibility, resulting from ‘wrong’ blood to ‘wrong’ patient

Small (20 ml) inoculation causes symptoms of fever, substernal/loin pain, hypotension, dyspnoea, flushing,

haemoglobinuria, DiC

StoP traNSFUSioN

Maintain renal perfusion with fluids (35% risk of renal failure), oxygen therapy

Supportive treatment. transfer to HDU/itU and seek specialist help

Delayed haemolytic


Haemolysis generally extravascular owing to Kidd and Duffy incompatibility

Fever, jaundice, haemoglobinuria presenting 5–10 days after transfusion

Less commonly hypotension and renal failure

rarely fatal

Urticarial and

anaphylactic reactions

reactions may be anaphylactic or anaphylactoid and should be managed according to standard allergic reaction

protocols. investigation of the cause will guide subsequent management

Bacterial contamination endogenous contamination due to a bacteraemia donor may lead to infections such as Treponema pallidum

(syphilis)

exogenous contamination of blood pack during processing risks transfusion of Pseudomonas and Staphylococcus

Post-transfusion purpura this rare cause of immune destruction of both transfused and host platelets occurs 7–10 days after transfusion. it

is usually self-limiting but plasma exchange ± immunoglobulin may be needed

immunomodulation transfusion results in both temporary and long-term stimulatory and suppressive changes in immune function in

the recipient

recurrent spontaneous abortions rates are increased in females

Colorectal tumour recurrence may be increased by as much as 37%. this may occur, but is less well defined in

other tumours

transfusion-associated

graft vs host disease

although rare, this is almost always fatal as there is no effective treatment

immunodeficient patients develop a rash, diarrhoea, liver failure, leading to marrow failure and pancytopenia

Death occurs within 3–4 weeks following infection

γ-irradiation of blood reduces the risk

transfusion-transmitted

infections

infectious agents of several types reported to have been transmitted

viral: Hiv, hepatitis a, B, C and D, CMv, HtLv i and ii, eBv

Bacterial: syphilis, Lyme disease, brucellosis, salmonella

Protozoan: malaria, toxoplasmosis

transfusion-related

acute lung injury

See text

CMv, cytomegalovirus, DiC, disseminated intravascular coagulation; eBv, epstein–Barr virus; HDU, high-dependency unit; HtLv, human t-lymphotropic virus.

Table 8

Reports are published annually detailing causes of mortality and morbidity and the data are used to make evidence-based and targeted recommendations or improvements in transfusion practice.

The 2006 SHOT report: In the financial year April 2005-6 2.5 mil-lion units of blood were issued from transfusion services in the UK. There was a 13% reduction in the number of reports in existing SHOT categories compared with 2005. ABO incompatible transfu-sions were lower than ever recorded; 8 cases with no fatalities.

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Prescription errors by doctors were prominent with 125 reported incidences; 2 resulting in death. As a consequence it has been recommended that transfusion medicine becomes part of core UK medical school curriculum.

Two other deaths occurred - one following administration of platelets infected with Klebsiella pneumoniae and one from TRALI. 400 events of incorrect blood component transfusion were reported. This represents an incidence of 10.6 reports per 100,000 components transfused, verses a rate of 12.8 in 2005 report.


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Autologous blood transfusion

Concerns over transmission of infection following allogeneic blood transfusion have led to interest in this area. It is also a useful practice for managing patients with rare blood groups and demand on allogeneic transfusion services can be reduced. This approach is not without risk and administration of a safe and efficient service is costly. Its use should be restricted to situations of anticipated blood loss of >20% blood volume. Unused blood is not suitable for return to the national donor pool and there-fore must be discarded. Three methods are currently available for autologous transfusion.

Cell salvageCell salvage is the most commonly used method in the UK. Shed blood is collected during and after surgery, ‘washed’ with saline and separated from debris by centrifugation to form a concen-trated transfusable product.

Cell salvage has an excellent safety record and blood loss is virtually matched with supply. Complications can arise from electrolyte disturbances and dilutional coagulopathy. Pyrexia

Complications of massive blood transfusion

Complication Details

Hyperkalaemia arrhythmias

Hypocalcaemia due

to citrate toxicity

abnormal liver function/perfusion slows

citrate metabolism

Monitor ionized calcium on blood gas

analyser

treat with 10 ml of 10% calcium chloride

(not gluconate which requires hepatic

metabolism for calcium liberation)

Hypothermia Warm blood, especially in massive

transfusions

impaired oxygen

delivery

right shift of the oxygen dissociation

curve is effected by acidosis and

hypothermia

acidosis Control with bicarbonate only in extreme

cases

Coagulopathy Pt and aPtt should be maintained at

< 1.5 × control

Consider FFP after 1 × blood volume

replacement

Maintain fibrinogen at >1.0 g/litre

thrombocytopenia Maintain at >75 × 109/litre

anticipate transfusion after two blood

volume replacements.

Clerical error emergency situation increases risk of

wrong blood to wrong patient

transfusion-related

acute lung injury

rare. See text

aPtt, activated partial thromboplastin time; FFP, fresh frozen plasma; Pt, prothrombin time.

Table 9

SUrGerY 26:9 39

and shivering may occur in up to 12% cases as a consequence of inefficient blood washing.

Cell salvage is contraindicated in the presence of sepsis and from contaminated surgical fields (e.g. bowel surgery). Its suit-ability for use in malignant disease remains unclear because of concerns that transfused malignant cells may disseminate the malignancy. The consequence of transfusing amniotic fluid and foetal cells to obstetric patients is similarly undefined.

Preoperative autologous donationPreoperative autologous donation (PAD) is a less common prac-tice in the UK. Patients donate blood for blood bank storage and for their exclusive use in advance of planned surgery. Donations are usually given over a 5 week period with 400–500 ml being harvested on each occasion. Blood can only be stored for 5 weeks and the last donation must be no less than 72 hours - preferably no less than 7 days - before surgery.

It has been shown that oral iron supplements will increase the blood yield even in non-iron deficient patients and is recom-mended. While erythropoetin is licensed for use in this indication its use is limited by high cost and the increased thrombotic risk.

PAD has been shown to reduce the number of allogeneic units used, but is associated with an increased likelihood of transfu-sion, which exposes patients to risks such as administrative errors, fluid overload and sepsis. Difficulty in predicting blood requirements leads to high blood wastage rates.

Acute normovolaemic haemodilutionVenous blood is drained into bags containing citrate immediately prior to surgery and replaced with crystalloid or colloid infusion. Consequently, blood shed during surgery will have a lower hae-matocrit. The harvested blood is returned to the patient towards the end of the operative procedure. The units are not subject to microbiological tests and should be treated and labelled as being ‘high risk’; they must not to be stored in blood bank refrigerators for risk of them entering the hospital blood pool. Unused blood is discarded at the end of the procedure.

Blood transfusion and the Jehovah’s Witness

Every competent adult is entitled to refuse medical treatment. Allogeneic blood transfusions (whole blood, packed red cells, FFP and platelets) and preoperative autologous blood collec-tion are regarded as unacceptable to Jehovah’s Witnesses. Each patient may make a personal choice regarding blood salvage, plasma fractions (albumin, immunoglobulins, clotting factors) and organ transplantation.

The key to successful management of this group is good com-munication between senior staff involved in the care, the patient and their community elders, who can be invaluable in provid-ing guidance. Discussions should be fully documented and the patient’s views must be explicitly recorded and witnessed. Flout-ing documented wishes may place a clinician at risk of disci-plinary action and may be considered a criminal offence. Many Witnesses carry advanced directives, or lodge them with their general pratctioner, which may help guide emergency treatment.

The situation for the children of Jehovah’s Witnesses is com-plex and there are minor variations in the procedure required between England and Wales and both Scotland and Northern


PerioPerative

Ireland. In most cases application for a court order will be made. It is worth noting that in each of these countries, a child over 16 may override the wishes of their parents with regard to their own treatment. In the emergency situation, where it can be convinc-ingly shown that a child will die without immediate blood admin-istration, the courts are likely to uphold the decision of a doctor in doing so. The situation in other countries will vary and each clinician should be aware of local and national guidance. ◆

REFERENCES

1 Choi P, Yip G, Quinonez L, Cook D. Crystalloids versus colloids in

fluid resuscitation: a systematic review. Crit Care Med 1999; 27: 200–10.

2 Schierhout G, roberts i. Fluid resuscitation with colloid or crystalloid

solutions in critically ill patients: a systematic review of randomised

trials. BMJ 1998; 316: 961–4.

SUrGerY 26:9 391

FuRTHER READING

Guyton aC, Hall Je. textbook of medical physiology, 11th edn.

Saunders, elsevier Health Sciences, 2005.

Murphy M, Pamphilon, eds. Practical transfusion medicine. London:

Blackwell Science, 2001.

Serious Hazards of transfusion (SHot). also available from:

http://www.shotuk.org June 2008.

the albumin reviewers (alderson P, Bunn F, Li Wan Po a, Li L, roberts

i, Schierhout G). Human albumin solution for resuscitation and

volume expansion in critically ill patients. Cochrane Database Syst

rev 2004, issue 3. art. No.: CD001208. Doi: 10.1002/14651858.

CD001208.pub2.

the SaFe Study investigators. a comparison of albumin and saline for

fluid resuscitation in the intensive care unit. N Engl J Med 2004;

350: 2247–56.

William F, Ganong MD. review of medical physiology, : McGraw-Hill,

2005.


http://www.shotuk.org

fluid and electrolyte balance, anaemia and blood transfusion

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