Blood transfusion free management

• REDUCE IATROGENIC BLOOD LOSS
• MAXIMISE OXYGEN DELIVERY
• MINIMISE OXYGEN CONSUMPTION
• IMPROVE BLOOD COUNT
• PRE-OPERATIVE WORKUP/CLINICAL EVALUATION
• SURGICAL/ANAESTHETIC BLOOD CONSERVATION TECHNIQUES

1. MINIMISE HAEMORRHAGIC BLOOD LOSS

• Avoid hypertension and hypervolaemia. If active bleeding present, consider tolerating mild hypotension (i.e., reduced systolic blood pressure in the range of 90 - 100 mm Hg for a normotensive patient) until haemorrhage is promptly controlled, using a combination of blood conservation modalities. Hypertension and hypervolaemia may inhibit spontaneous haemostasis, accentuate haemorrhage, or disrupt effective thrombus. Excess fluids may also promote haemorrhage by diluting coagulation factors and lowering blood viscosity. Allow a slow, gradual return to normal blood pressure after bleeding is controlled. In resuscitation from shock state avoid circulatory overload. Fluid administration by protocol without any ongoing clinical judgement should be avoided. Use vasodilators to manage hypertension with/without automated control of transient hypertension.

• Avoid severe hypotension. Use vasoactive drug therapy to control marked hypotension not responding to fluid therapy. In severe head trauma, maintain appropriate level of cerebral perfusion pressure (i.e. 70-80 mm HgCPP). Resuscitation of head-injured, multiply-traumatised patients with lactated Ringer's, hypotonic, or dextrose-containing solutions may be detrimental.

• Maintain extra vigilance to detect and treat ongoing bleeding and other complication. Note: Continuous low-level bleeding (e.g., from small vessels and capillaries) could become significant if tolerated for a prolonged period of time.

• Avoid delay. Do not defer surgery if active bleeding cannot be controlled non-operatively (e.g., pharmacologic, endoscopic, angiographic).

• Blood salvage (i.e., post-operative).

• Maintain normothermia unless hypothermia is indicated.

Notes:

1. External active warming may be superior to passive warming.
2. Coagulation proteins may be less effective at lower temperatures, increasing risk of blood loss.
3. Hypothermia is associated with higher infection rates.
4. Controlled hypothermia may be considered for severe anaemia or cerebral protection.

• Haemostatic agents for bleeding/clotting problems

• Tranexamic acid
• Epsilon-aminocaproic acid
  Desmopressin (use trial dose to assess response)
• Aprotinin
• Note: Aprotinin or desmopressin may reduce bleeding due to drug-induced platelet dysfunction (e.g., due to aspirin, NSAIDs, beta-lactam antibiotics, antithrombotics).
• Conjugated oestrogens
• Vasopressin
• Appropriate drugs to control gynaecological haemorrhage (e.g., hormone manipulation)
• Vitamin K

Notes:
1. Consider prophylactic parenteral administration of vitamin K.
2. Causes of vitamin K deficiency include:
a. Inadequate dietary intake, limited absorption or synthesis
b. Antibiotics
c. Anticoagulants (e.g., Warfarin, nicoumalone)
d. Other drugs (e.g., salicylates)
Treatment for congenital or acquired haemorrhagic disorders:
a. Clotting factor replacement therapy

Note:
Factors VIIa, VIII, IX are available as recombinant products.
b. Cryoprecipitate
I. Prophylaxis of upper gastrointestinal haemorrhage
Cytoprotective agents (e.g., sucralfate)
Enteral nutrition
Proton pump inhibitors
H2 blockers (associated with thrombocytopenia and pancytopenia in some patients; may reduce iron solubility due to increase in gastric pH).

• Avoid/treat infections promptly. Prophylaxis of infection. Thorough assessments of wounds; avoid secondary contamination (e.g., colon or rectal)

2. REDUCE IATROGENIC BLOOD LOSS

1. Perform only essential tests
2. Eliminate duplication/perform multiple tests per sample
3. Paediatric phlebotomy tubes
4. Point-of-care whole blood microsampling
5. Pulse oximetry
6. Transcutaneous oximetry
7. End-tidal CO2 monitoring
8. In-line blood reservoirs; eliminate purge discard volume
9. In-line arterial blood gas monitors

1. Consider dosage reduction, discontinuation, or substitution with alternative medication. Continue monitoring for adverse reactions.
2. Judicious prophylaxis of thromboembolism. Closely monitor patients treated with anticoagulants/antiplatelet drugs. Risk of haemorrhage is related to dosage, duration of therapy, and predisposing conditions where risk of haemorrhage is present.

3. MAXIMISE OXYGEN DELIVERY

• 1. Judicious use of asanguineous fluids:
• a. Crystalloids
  i. Ringer's lactate
  ii. Normal saline
  iii. Hypertonic saline
• b. Colloids
  i. Pentastarch
  ii. Hetastarch (may adversely affect coagulation - see note 3 below)
  iii. Gelatin
  iv. Dextran (may adversely affect coagulation - see note 3 below)
• c. Perfluorochemicals (oxygen-carrying blood substitutes)

1. Normovolaemic anaemia can be tolerated in haemodynamically stable patients.
2. Avoid circulatory overload, especially in profoundly anaemic patients. Closely monitor fluid balance and vital signs.
3. The clinician should judiciously choose the solution(s) for volume expansion.
4. In cases where clinical examination and non-invasive investigation may provide inadequate date, use invasive monitoring (e.g., central venous line, arterial catheter, pulmonary artery catheter,) to guide the management of patients.
5. Bleeding should be considered and diagnosis sought when a patient shows evidence of hypovolaemia despite reasonable hydration. Avoid aggressive fluid replacement to normalise blood pressure. Adequate perfusion can be obtained at lower pressure. Simple measurement of vital signs is a poor indicator of blood volume loss.
6. Albumin therapy may be detrimental to the shocked patient.

1. 1. Closely monitor and assess oxygen utilisation/hypoxia (e.g., clinical signs, pH and lactate, urine output), haemodynamics (e.g., cardiac output, pulmonary artery wedge pressure).
2. Maintain/improve tissue perfusion and cardiac output (fluids and inotropes).
3. Maintain blood pressure (fluids and vasopressors).

1. Appropriate and adequate ventilatory support for optimal oxygenation and CO2 elimination (e.g., CPAP, IPPV, PEEP).Note: Nitric oxide and hypercapnia may increase risk of bleeding.
2. Ongoing monitoring and assessment of the adequacy of ventilation and oxygenation (clinical assessment, arterial blood gas analysis and/or pulse oximetry, capnometry, oximetric pulmonary artery catheter) to allow for early and appropriate intervention.
3. Hyperbaric Oxygen Therapy (HBO)a. Indications for HBO therapy:
   i. Adequate oxygen transport (arterial and mixed venous blood gas analysis) cannot be achieved using conventional mechanical ventilation
   ii. Tissue hypoxia (e.g., mental confusion, abnormal vital signs, decreased urine output, metabolic acidosis) in the presence of adequate fluid resuscitation and perfusion.
   b. Use ongoing monitoring to determine appropriate HBO dosage and onset of adverse effects (e.g., pulmonary and CNS function).
   c. Use intermittent HBO therapy to minimise oxygen toxicity or barotrauma.
   d. Provide concomitant therapy with i.v. r-HuEPO, and iron, folate, and nutrition to support haematopoiesis.

4. MINIMISE OXYGEN CONSUMPTION

A. Adequate and appropriate analgesia
B. Sedation; consider neuromuscular blockade (i.e., to prevent muscle shivering, agitation, anxiety).

1. To minimise adverse effects, use lowest dose and shortest duration of analgesia and sedation necessary.
2. Closely monitor degree of blockade (e.g., peripheral nerve stimulation) and adjust drug doses to determine minimum appropriate dosage to allow faster recovery of neuromuscular function and spontaneous ventilation; avoid standard dosing.

C. Mechanical ventilation
D. Maintain/restore normothermia unless hypothermia is indicated. Actively rewarm post-operative patients. Cool febrile patients.

5. IMPROVE BLOOD COUNT

1. i.v. Iron (use test dose)
2. Folic acid
3. Vitamin B12
   

Notes:

1. Intravenous route of administration improves bioavailability, rapidly increases stores, avoids potential malabsorption of gastric irritation (e.g., oral iron).
2. Concomitant administration of ascorbic acid and oral iron may enhance absorption from the gastrointestinal tract.
3. Oral iron is known to interact with many commonly used drugs.

1. Subcutaneous injection or intravenous administration
2. Factors that may delay or attenuate response to r-HuEPO include:

a. Iron deficiency
b. Chronic infection, inflammation, or malignant process
c. Occult blood loss
d. Bone marrow disease
e. Vitamin deficiencies (folate, B12)
f. Poor subcutaenous absorption of r-HuEPO
g. Haemolysis
h. Aluminum intoxication (e.g., medications, dialysate fluid)
i. Hyperparathyroidism

1. Endogenous EPO production is proportional to degree of anaemia. For severe anaemia, r-HuEPO should be used for rapid restoration of red cell mass.
2. A high endogenous EPO level does not preclude response to r-HuEPO.
3. Rate of response to r-HuEPO is dose dependent and varies among patients. Therapy may need to be individualised. Monitor and escalate dosage or change route of administration to improve response.
4. Consider pre-treatment investigation to identify and correct, if possible, any factor that could mediate erythropoietin resistance. If not correctable use higher dose.
5. Hyperoxic ventilation (a high PaO2) or critical illness may blunt endogenous EPO production in response to acute anaemia.
6. r-HuEPO administration up to 2,000 U/kg/day in divided doses has been reported to be well tolerated.
7. Monitor for hypertension, which may induce bleeding, and consider initiation or increases in antihypertensive therapy.
8. r-HuEPO may produce a moderate dose-dependent rise in the platelet count, within the normal range, during treatment.

PRE-OPERATIVE PLANNING

6. PRE-OPERATIVE WORKUP/CLINICAL EVALUATION

1. History of anaemia
2. Congenital/acquired bleeding disorders (suspected by reviewing obstetric history, circumcision, frequent nose bleeds, easy bruising without trauma, tonsillectomy, dental extraction, menorrhagia, prolonged bleeding after minor skin lesion, previous surgery, pregnancy, etc.).
   a. Personal history
   b. Family history
3. End-organ disease/injury (esp renal or hepatic)
4. Previously surgery (blood loss may be increased with repeat surgery)
5. Identify medications that may adversely affect haemostasis (e.g., aspirin, NSAIDs, anticoagulants, platelet aggregation inhibitors, antibiotics, dietary supplements). Also ensure that additional prescription and non-prescription drugs containing aspirin or NSAIDs are not inadvertently taken by patients.
6. Physical exam (e.g., purpuric lesions, petechiae, ecchymosis, hepatomegaly, splenomegaly)

1. Establish baseline parameters:
   a. Complete blood count (including red blood cell and platelet counts)
   b. Serum ferritin
   c. Serum folate
   d. Serum vitamin B12
   e. PT, PTT, template bleeding time (as indicated)
2. Additional investigation as indicated by history and degree of haemostatic challenge:
   a. Coagulation tests
   i. Platelet function, adhesion, aggregation tests
   ii. Fibrinogen concentration
   iii. Fibrin degradation products (FDP)
   iv. Specific coagulation factor assays
   v. Assay for ristocetin cofactor activity (von Willebrand disease, Bernard-Soulier syndrome)
   b. Liver function
   c. Renal function (creatinine)
   d. Point-of-care coagulation monitoring (e.g., thrombelastogram, Sonoclot)Note: Minimise iatrogenic blood loss. (See 2. A.)
   

1. Consider discontinuing medications associated with increased post-operative bleeding complications (from 3 to 14 days pre-operatively) and temporary substitution with alternate therapy (e.g., NSAIDs with short half-lives, heparin):
   a. Aspirin (at least 7 days before surgery)
   b. NSAIDs (10 days or more for NSAIDs with long half-lives)c. Anticoagulants, platelet inhibitors (e.g., Warfarin, ticlopidine)
   d. Antibiotics (e.g., ticarcillin)
2. Treatment for congenital/induced haemorrhagic disorders (See 1. H.)
3. Consider pre-operative prophylactic optimisation of tissue perfusion by augmentation of cardiac output (patients with coexisting pathology and poor cardiac function).

1. Minimally invasive techniques (endoscopic/laparoscopic surgery)
2. Enlarged surgical team/minimal time
3. Surgical positioning to minimise bleeding
4. Staged surgery for complex procedures
   B. Arterial embolisation (including pre-operative)
   C. Meticulous haemostasis
   D. Mechanical occlusion of bleeding vessel
   E. Electrocautery
   F. Ultrasonic scalpel
   G. Argon beam coagulator
   H. Tissue adhesives
   I. Intraoperative blood salvage
   J. Haemodilution
   K. Platelet-rich plasma sequestration
   L. Induced hypothermia
   M. Hypotensive anaesthesia