Blood

Giving blood carries a small risk and uses a valuable resource. The trend is more towards giving blood only when absolutely necessary. The following are indications for blood transfusion:

• to expand intravascular volume in serious haemorrhage

• to restore oxygen carrying capacity.

The decision to transfuse blood for anaemia depends very much on volume status, ongoing blood loss, and any preexisting myocardial or cerebrovascular ischaemia rather than on an absolute haemoglobin. Blood may be required in life-threatening haemorrhage even if the haemoglobin is normal. On the other hand, stable patients can tolerate anaemia well via compensatory mechanisms and consideration of blood transfusion in these patients is usually only appropriate when the Hb falls below 8 g dl-1.

Stored whole blood has a haematocrit of 40% but plasma, platelets, and other components are removed, leaving concentrated red cells with a haematocrit of 60%. It can be stored at 1-6°C for 28 days. Acid citrate dextrose is one of the most common additives to prevent clotting. The acid acts as a buffer, the citrate binds calcium, which inhibits clotting, and the dextrose acts as a substrate for red cells. Platelets reduce to virtually zero after 24 hours of storage and clotting factors V and Vlll are reduced to 50% after 21 days.

• O negative blood is immediately available.

• Type-specific blood (group and rhesus state only) is ready in 5 minutes.

• Fully cross-matched blood is ready in 20 minutes.

The risks of transfusion decrease with more specific matching. Transfusion reactions are rare but can occur with only small amounts of blood. Death occurs in 1 in 100 000 transfusions. Reactions range from fever to haemolytic syndromes, acute renal failure, and anaphylaxis.

Complications of blood transfusion are immunological, infective, metabolic, or general (for example, hypothermia and fluid overload) and there are further complications with large blood transfusions (Box 5.1).

Box 5.1 Complications of blood transfusion.

Immunological

• Haemolysis, immediate or delayed

• Anaphylaxis

• Increased risk of infection and recurrence or cancer postoperatively

Infective

• Rarely, red cells may become contaminated with bacteria during storage. There is rapid development of sepsis and cardiovascular collapse.

• UK blood is screened for hepatitis B and C, HIV-2 and syphilis. Donors undergo rigorous health screening with several exclusion criteria. Since 1998, 95% of white cells are removed because of a theoretical risk of nvCJD transmission.

Metabolic

• Potassium, calcium and acid-base balance may be affected.

Massive blood transfusion (for example, 10 units within 6 hours) has particular problems in addition to those of transfusion generally:

• Coagulopathy

• Hypothermia

• Hypocalcaemia

• Hyperkalaemia

• Metabolic acidosis followed by metabolic alkalosis from citrate

• ARDS (acute respiratory distress syndrome)

Many blood transfusions are given to treat a haemoglobin level rather than the patient. One randomised Canadian study (TRICC) looked at two groups of stable patients in ICU. In the first group, blood transfusion was triggered at a haemoglobin of 7 g dl-1 and maintained at 7-9. The second group was transfused if the haemoglobin fell below 10 g dl-1 and was maintained at 10-12. There was no advantage for the patients with higher haemoglobins and blood transfusions were reduced by 54% overall. At the time of writing one unit of blood costs £72 in the UK. The TRICC study found a survival advantage in the lower haemoglobin group among certain subgroups of patients. A lower haemoglobin conferred an advantage if the APACHE II score was < 20 and the age was < 55.

A recent study published in the journal JAMA looked at blood transfusions in ICUs across Europe. Transfused patients had a significantly higher mortality despite similar disease severity scores. The authors suggested that red cell transfusions may contribute to immunosuppression.

Studies have shown that perioperative blood transfusion increases the risk of infectious complications after major surgery and of cancer recurrence after curative surgery. This is thought to be related to the immunosuppressant effects of allogeneic blood transfusion and the fact that stored blood contains angiogenic factors.

Mini-tutorial: the crystalloid versus colloid debate

Despite much debate concerning the choice of fluid in volume resuscitation, the crystalloid versus colloid debate has largely reached a stalemate. During the World War II, surgeons realised that salt and water are retained after surgery and it became common practice to restrict them. There were subsequent problems with volume depletion because third space losses were not appreciated. In the 1960s studies showed that patients who received crystalloid and blood did better than patients who only received blood. Shire showed in animal experiments, using radioactive tracers, that the interstitial compartment contracts during trauma and major surgery. Crystalloids not only resuscitate the intravascular compartment, they resuscitate this compartment as well, but large volumes of crystalloid are needed to resuscitate the intravascular compartment because they are quickly distributed throughout the ECF - this can lead to problems with interstitial oedema when large amounts of crystalloid are given. With the advent of synthetic colloids, many people believed these were better, because they were more effective at expanding the intravascular compartment. They are faster to give, with less sodium load and risk of hypothermia, and a more rapid expansion in plasma volume restores tissue perfusion quickly, which can prevent tissue damage and the subsequent release of inflammatory mediators. However, allergic reactions can occur and colloids are more expensive. Studies have shown no difference in mortality but the cost per life saved using colloids is much more.

All the studies that have been done comparing crystalloids and colloids have yielded conflicting results. Extensive research has failed to show the superiority of colloids or crystalloids. Most colloid advocates do not recommend colloids as the only fluid to be used in resuscitation. It may be that certain subgroups of patients benefit from one type of fluid over another - but there is no definitive answer and the debate goes on.

Mini-tutorial: controversies over albumin

A recent Cochrane review looked at human albumin administration in the critically ill and its effects on mortality. The results were widely publicised; 30 trials met the inclusion criteria (1419 patients). The investigators found that the risk of death for patients receiving albumin was 14% compared with 8% in controls - or that for every 17 critically ill patients treated with albumin there was one additional death. The validity of the studies included in the systematic review was extensively debated. A later publication pointed out that more than half the trials included were pre-1990 and did not reflect current practice. The trials also included a mixture of patients with different characteristics and many were not blinded. Nevertheless, the debate did spark a controversy and probably contributed to a reduction in albumin use.

Albumin is sometimes given to treat hypoalbuminaemia, which occurs in critical illness. This has not been shown to improve outcome when compared with that for synthetic colloids. Albumin leaks from the circulation in critical illness, but serum albumin levels do not correlate with the osmotic pressure of the intravascular compartment. Studies have shown similar osmotic pressures in critically ill patients with low versus normal albumins. However, albumin administration reduces mortality when given in spontaneous bacterial peritonitis and is also used in the hepatorenal syndrome. None of the controversy around albumin applies to its evidence-based use in liver disease.

Self-assessment - case histories

1. A 60-year-old man returns to the ward, having had a laparotomy for bowel obstruction which lasted 2 hours. You are informed that his urine output for the last 2 hours has been < 30 ml h-1. In theatre he received 1 litre of Hartmann's and 1 litre of Gelofusine. His vital signs are: pulse 80 per minute, blood pressure 140/70 mmHg, respiratory rate 20 per minute, and core temperature 37-5°C. The nurse is concerned about his urine output. How do you assess his volume status?

2. A 55-year-old man is on the coronary care unit when he develops a low urine output (< 0-5 mg kg-1 per hour for the last 2 hours). His vital signs are: pulse 90 per minute, blood pressure 110/50 mmHg, respiratory rate 22 per minute, and core temperature 37°C. He has cool hands and feet. He had an inferolateral myocardial infarction 24 hours ago. The nurse is concerned about his urine output. How do you assess his volume status?

3. A young woman arrives in the medical admissions unit with diarrhoea, which she has had for several days. She also has a macular rash and a high fever. She has a systolic blood pressure of 70 mmHg and a pulse of 130 per minute. Her blood tests show an elevated urea and creatinine with low platelets. What is your immediate management?

4. A middle-aged man comes to the Emergency Department having fallen on the path and hurt his left lower ribs. His observations are: pulse 110 per minute and blood pressure 140/90 mmHg. You notice how clammy he feels to touch. Could this man have a life-threatening haemorrhage?

5. An 80-year-old lady is admitted with abdominal pain and malaena. She has a permanent pacemaker and is treated for congestive cardiac failure, which is under control. Her pulse and blood pressure are normal. How can you assess her volume status?

6. A 50-year-old man weighing 70 kg with no past medical history is admitted with gastric outflow obstruction and is scheduled for surgery later in the week. His fluid balance chart for the last 24 hours is as follows. Input: nil orally, 3 litres intravenous 0-9% sodium chloride. Output: urine 500 ml total, bowels nil, nasogastric tube 4000 ml total. There are no intravenous antibiotics or other drugs, and no fever is recorded. This morning's blood results show: Na 150 mmol litre-1, K 3-0 ^mol litre-1, urea 12 mmol litre-1 (33-3 mg dl-1), creatinine 140 ^mol litre-1 (1-68 mgdl-1). What fluids should you prescribe for the next 24 hours?

7. A patient comes back from theatre to your high dependency area. His vital signs are: pulse 80 per minute, blood pressure 150/80 mmHg, respiratory rate 25 per minute, and core temperature 36°C. His arterial blood gases show: pH 7-3, PaO2 15-0 kPa (115 mmHg), PaCO2 4-0 (29 mmHg) and bicarbonate 14-5 mmol/l, BE - 6. His CVP reading is 12 mmHg. He received Hartmann's and blood in theatre. How do you manage his acidosis?

8. A patient on ICU with a tracheostomy has been on maintenance crystalloid (0-9% saline) for several days and this morning's blood results show: Na 145 mmol litre-1, K 4-0 mmol litre-1, urea 4-5 mmol litre-1 (12-5 mg dl-1), creatinine 80 ^mol l-1 (0-96 mg dl-1). The patient is stable and the vital signs are: pulse 60 per minute, blood pressure 130/65 mmHg, respiratory rate 12 per minute and core temperature 36-5°C. The arterial blood gases show: pH 7-3, PaO2 13-0 (100 mmHg), PaCO2 4-5 (34-6 mmHg) and bicarbonate 16-3 mmol/l, BE - 5. The patient is doing well in every way and is expected to leave ICU in the next 24 hours. The examination is normal. Can you explain the arterial blood gas results?

9. You have just put a CVP line into a patient who is unwell with a severe biliary infection. The CVP measures 15 mmHg. What is your next course of action?

10. A postoperative patient's blood results are as follows: Na 120 mmol litre-1, K 4-0 mmol litre-1, urea 6-0 mmol litre-1 (16-6 mg dl-1), creatinine 95 ^mol l-1 (1-14 mg dl-1). How do you assess the low sodium in order to treat it correctly?

Self-assessment - discussion

1. The history alone in this case tells you that the patient is likely to be hypovolaemic - he has a history of bowel obstruction and has just had a laparotomy, so is likely to have a combination of hypovolaemia with capillary leak and interstitial oedema. Check skin temperature and capillary refill at the peripheries as it may be reduced if there is hypovolaemia. His respiratory rate is raised. Arterial blood gases may reveal a base deficit suggesting tissue hypoperfusion. A fluid challenge should be given if there are signs of hypovolaemia or if there is any uncertainty about his volume status. This kind of patient should never be given a diuretic as first-line treatment for a poor urine output. It would be appropriate to give 250 ml colloid over 10 minutes and assess the response.

2. Patients admitted to hospital following a myocardial infarction can be dehydrated due to vomiting, sweating, and reduced oral intake. His respiratory rate is raised and his peripheral skin temperature may be reduced. In this case, you would want to know if there are any crackles audible in the lungs. Arterial blood gases may reveal a base deficit. A fluid challenge can be given safely if there are signs of hypovolaemia or if there is any uncertainty about this patient's volume status. The definition of cardiogenic shock includes a low cardiac output state, which is unresponsive to fluid (see Chapter 6) and this implies that fluid is used in the assessment of this condition.

3. The picture is of a young person with severe sepsis. A search for the focus of infection should take place but this should not take priority over A, B, C, and "blind" antibiotic therapy. After you have initiated high concentration oxygen therapy, two large bore cannulae should be inserted and fluid challenges given. There is a history of diarrhoea for several days, which implies severe volume depletion - but in the context of severe sepsis, an abnormally low systemic vascular resistance means that the hypotension may not respond to fluid alone, and invasive monitoring and vasopressors may be required.

4. Yes. It is highly possible that this man has ruptured his spleen. Airway is okay. Check breathing (for pneumothorax) and insert two large bore cannulae for fluid. Assess capillary refill. He could have lost 20-30% of his circulating blood volume already and needs urgent imaging and surgery.

5. This is exactly the type of patient in whom volume status can be incredibly difficult to assess. The elderly do not respond physiologically to bleeding in the same way as younger patients. The history of a gastrointestinal bleed points to volume depletion, as does chronic diuretic use. Although she has a "normal" blood pressure - is it her normal? Special attention must be paid to other markers of hypoperfusion in this lady, as pulse and blood pressure (including orthostatic measurements) will be of little value. Look at peripheral skin temperature and respiratory rate, and perform an arterial blood gas analysis. A urinary catheter should be inserted to monitor hourly urine output.

6. The blood tests and the fluid balance chart suggest volume depletion. Large nasogastric losses have resulted in hypokalaemia. In a dehydrated patient with hypernatraemia, total body water deficit may be calculated as follows:

Volume in litres needed = 0-5 x

0-5 is the approximate total body water (TBW). In this patient the TBW deficit is 3-57 litres (Table 5.7). This is required over the next 24 hours in addition to his maintenance requirements and anticipated ongoing nasogastric losses. Hartmann's at 110 ml h-1 is appropriate as maintenance fluid; 5% dextrose with additional potassium can replace water losses - 4 litres can be given in addition to the Hartmann's over the next 24 hours.

Table 5.7 Daily volumes and electrolyte contents (mmol litre-1) of body secretions

Body secretions

ml 24 h-1

Na2+

K+

Cl-

HCO3-

Saliva

+ 1500

10

25

10

30

Stomach

+ 1500

50

10

130

0

Duodenum

+ 1000

140

5

80

0

Ileum

+ 3000

140

5

104

30

Colon

- 6000

60

30

40

0

Pancreas

+ 500

140

5

75

100

Biliary

+ 500

140

5

100

30

Sweat

+ 1000

50

0

0

0

7. The history tells you that the metabolic acidosis is most likely due to lactate because of hypoperfusion. Other markers of hypoperfusion should be checked - peripheral skin temperature, respiratory rate, and urine output. "Normal" blood pressure, pulse, and CVP readings do not exclude hypovolaemia. Fluid challenges should be given and the response assessed. Patients returning from theatre often have a reduced core temperature and as they rewarm, vasodilatation causes relative hypovolaemia, which requires fluid. A metabolic acidosis that worsens rather than improves with fluid therapy and rewarming suggests a problem in the abdomen (bleeding or ischaemia) which needs urgent investigation.

8. Prolonged infusions of 0-9% sodium chloride can lead to a hyperchloraemic metabolic acidosis. Controversy has surrounded the aetiology and clinical relevance of the acidifying potential of large volumes of sodium chloride solutions. The term "dilutional acidosis" implies that plasma expansion and a consecutive dilutional reduction of plasma bicarbonate are the underlying mechanisms. In contrast others have suggested the importance of hyperchloraemia resulting in a reduction of the strong ion difference (SID), calculated as [Na] + [K] - [chloride] - [lactate].

9. The next course of action is to treat the patient on the basis of your assessment of volume status, not a single CVP reading. A fluid challenge should be given and the response of the CVP to this assessed. The "rule of threes" can be used.

10. Hyponatraemia results from salt losses alone or salt and water loss with water replacement. There are several causes of hyponatraemia and one should aim to treat the cause rather than simply fluid restricting the patient (Figure 5.7):

After clinical examination, plasma and urine osmolality and sodium levels should be measured.

• Serum osmolality high (>295 mosm kg-1) - "hypertonic hyponatraemia from hypoglycaemia, mannitol, or glycine irrigation;

• Serum osmolality normal - pseudohyponatraemia;

• Serum osmolality low (<280 mosm kg-1) - "hypotonic hyponatraemia"

Hypotonic hyponatraemia

Assess volume status

Hypovolaemia

• Diarrhoea and vomiting

• Dehydration

In volume depletion urinary Na+ is < 20 mmol litre-1

• Renal salt loss owing to drugs, renal disease or mineralocorticoid deficiency (urinary Na+ is > 20 mmol litre-1)

Euvolaemia

• Syndrome of inappropriate ADH secretion

• Postoperative

• Psychogenic polydipsia

Oedema

• Oedematous states, e.g. nephrotic syndrome, cirrhosis, and congestive cardiac failure

In oedematous states urinary Na+ is < 20 mmol litre-1

• Chronic renal failure (urinary NaJ is > 20 mmol litre-1)

Figure 5.7 Assessment of hyponatraemia

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