BLOOD CONSERVATION IN ANAESTHESIA AND

SURGERY

AGYA BOAKYE ATONSAH PREMPEH

OUTLINE

INTRODUCTION

BRIEF HISTORY OF BLOODLESS MEDICINE AND SURGERY

BLOOD CONSERVATION METHODS

FUTURE OF BLOODLESS MEDICINE AND SURGERY

INTRODUCTION

Bloodless Medicine and Surgery(BMS) is relatively new

Medicine has searched for alternatives to allogeneic blood

The term (BMS) is defined as the avoidance of allogeneic blood

The practice of BMS entails more

Balance - Benefits and risks Homologous blood transfusion

Knowledge of broad spectrum of techniques and methods Employment of those techniques and methods(condition&harm)

BRIEF HISTORY OF BLOODLESS MEDICINE AND SURGERY

During the second world war in the 1940s – Wounded soldiers

This subsequently led to an increased demand for blood donors

The practice of blood transfusion was regarded as an accepted therapeutic method by most

Not accepted by members of the religious organisation The Watch Tower Bible and Tract Society (Jehovah’s Witness) and same view

Founded in 1884 in Western Pennsylvania as a Bible Study Group

Grown into a worldwide organisation comprising over 7 million adherents in over 200 countries

The Witnesses’ belief is that God views blood as sacred and holy.

They cite some biblical passages to support their claims.

Leviticus 17:10-12, God says to Moses:

As for any man of the house of Israel or some alien resident who is

residing as an alien in their midst who eats any sort of blood, I shall

certainly set my face against the soul that is eating the blood, and I

shall cut him off from among his people.

Genesis 9:1-4, God says to Noah after the flood: Every moving animal that is alive may serve as food for you. As in the case of green vegetation, I do give it all to you. Only the flesh with its soul, its blood, you must not eat.

Bible does not speak of blood transfusion

The decree that Christians must abstain from taking blood covers the taking of blood into the body, whether through the mouth or directly into the bloodstream.

Initially, J.W. adamant refusal of blood and blood products was met with much controversy and frustration.

At the time the accepted ‘rule’ was to transfuse a patient if their haemoglobin was below 10g/dl or haematocrit was below 30%.

Doctors viewed J.W. position as one that prevented them from rendering adequate care under certain circumstances

A few physicians viewed their stance as just one more complication challenging their skill and was a unique opportunity.

In 1957 Dr Denton Cooley of the Texas Heart Institute pioneered open heart surgery without blood support

He led a team of cardiovascular surgeons who performed some 1250 ‘bloodless’ open-heart surgery on patients who requested it

In those days, most open-heart surgeries required 20-30 units of blood

It was the genesis of the bloodless medicine and surgery

However the programme BMS was officially launched in 1997 at USC University Hospital and USC Norris Cancer Hospital California in consultation with the local hospital liaison committee for J.W.

Large population of J.W. residing in California at the time

UNIVERSITY OF SOUTHERN CALIFORNIA HOSPITAL COMPLEX

Highlights of the USC Programme include:

The 1st adult-to-adult living-related live-donor liver transplant in a Jehovah’s Witness patient without blood products in June,1999.

Followed up with paediatric liver-donor liver transplant

Others include “bloodless”

o Radical nephrectomy

o Cystectomy

o Hip/Knee surgery

o Ortho-spine surgery

o Heart transplants

o Cardiac bypass and valve replacement surgery

Currently there about 100 BMS centres in the United States

The medical community is learning that bloodless medicine and surgery has some benefits:

1.Helps Patients avoid problems such as Risks of contracting blood-borne diseases → HIV, Hep A,B,C Blood transfusion reactions Shortage of blood

2. Patients also recover more quickly from surgical procedures (immunomodulation - down regulation of cellular immunity by allogeneic blood). Extensive data showing that it enhances renal allograft tolerance

3. Significantly reduce medical costs A study conducted by members of Cleveland Clinics Anaesthesiology Department concluded that using a bloodless surgery protocol 50% of the time, could save the health care industry in the US up to $3.7 billion a year.

BLOOD CONSERVATION METHODS

PRE-OPERATIVE MANAGEMENT

INTRAOPERATIVE STRATEGIES

POST OPERATIVE MANAGEMENT

PRE-OPERATIVE MANAGEMENT

This involves appropriately Assessing, Investigating and Preparing patients prior to surgery to aid in reducing or avoiding allogeneic blood transfusion

This is a multidisciplinary approach: Blood bank technician(PABD) Physician (hypertension) Haematologist (haematological disorders) Surgeon (surgical approach or composition of team) Anaesthetist (intraoperative technique that can be used)

ASSESS and if possible manage (prior to elective surgery)

Anaemia

Bleeding/Coagulation disorders

Cardio-respiratory disorders

SIGNIFICANCE OF ANAEMIA

Definition: Haemoglobin concentration in blood that is below the expected

value with respect to certain factors such as age, gender, pregnancy and altitude

The unit of measure is “g/dl” → value dependent on ratio between Total amount of circulating Hb in RBC (numerator) Plasma volume (denominator)

Hence variation in either of the two factors will affect Hb concentration

RISKS OF ANAEMIA IN SURGERY

Existence of underlying pathology Anaemia is not a diagnosis but an indication that an underlying

pathology exists Hence treating pathology and/or associated anaemia will improve the

patient’s pre-operative condition

Decreased oxygen reserve in the body Surgical blood loss or cardio-respiratory depression due to anaesthetic

agents leads to decreased oxygen carrying capacity of the blood Hence the body tries to maintain tissue oxygenation by falling on

oxygen reserves in the body. However in anaemic patients their oxygen reserves are diminished and hence are at a higher risk of decompensation

PHYSIOLOGICAL RESPONSE OF THE BODY TO ANAEMIA

Adequate tissue oxygenation is required to meet tissues’ metabolic demands in order to sustain life

This depends on the balance between oxygen delivery to the tissue and oxygen demand (consumption requirement) by the tissue

Amount of O2 consumed by tissue

Amount of O2

in arterial blood delivered to tissue

Amount of O2

in venous blood leaving tissue

n = (CaO2).(CO)

Bound to Hb (normally >98% of total O2)

Dissolved in plasma (<2% of total O2) (negligible in normal situation)

+

+1.34 x [Hb] x % saturation of Hb

0.003mlO2 / mmHg PaO2 / 100ml plasma

CaO2 = arterial oxygen content

CO = cardiac output

* (n = CV)

Major determinants of O2 delivery to tissue - [Hb], % saturation, CO , PaO2(diseased states)

The Maximum extraction of O2 by any tissue is about 15 vol %

i.e.15ml O2 per 100ml of blood delivered - ( kinetics of oxygen dissociation from

Hb)

Since our Cardiac output = 5000ml/min (on the average for an adult)maximum amount of O2/min that can be extracted body under basal conditions

5000ml x 15100ml

= = 750ml O2/min

BIPHASIC RELATION BETWEEN OXYGEN CONSUMPTION AND OXYGEN DELIVERY

A = oxygen delivery independent portion (irrespective of amount of O2 delivered, basal O2 consumption is maintained)

B = oxygen delivery dependent portion (amount of O2 delivered linearly determines O2 consumption) At this phase tissue hypoxia sets in with anaerobic metabolism → ↑ lactate levels)

DO2 critical

It is the minimum amount of O2 required to maintain tissue oxygenation

Below this threshold, tissue hypoxia sets in

The most rigorous clinical study found a threshold value of 4ml O2 /min/ kg (3-4g/dl Hb)

The(4ml O2/ min/kg) value isn't accurate because: The DO2 critical measures is based on the average anaerobic threshold for the whole body at rest Different organs in the body have different anaerobic thresholds which may vary significantly from the body’s average

Also metabolic demands are increased in various diseased states

Right Heart

Left Heart

Arterial side

Normovolaemia

Hypovolaemia(sympathetic response )

Venous side

NormovolaemiaHypovolaemia

Microcirculation

TISSUE

Post capillary venule

*NormovolaemiaHypovolaemia

Pre-capillary arteriole

*Normovolaemia *Hypovolaemia-

shunting

capillary flow*Normovolaemia -↑ flow leads to ↑ recruitment of previously closed capillaries*Hypovolaemia – decreased flow due to ↑viscosity↑ O2 extraction

Due to shift of oxyhaemoglobin curve2,3 diphosphoglycerate levels increases after 12-36hrs with declining Hb level

Lungs

ASSESSMENT AND MANAGEMENT(ANAEMIA/BLEEDING DISORDERS/CARDIORESPIRATORY DISORDERS)

HISTORY - Look out for common causes of Anaemia, Bleeding disorders and Cardiorespiratory disorders

1. Anaemia

↓ Production Erythrogenesis – renal disease leading to ↓ EPO Factory – BM failure (haematological failure) Raw materials

Iron – bleeding from orifices (menorrhagia, haematuria, bleeding PR) Folate - ↓ utilisation of folate (metformin, phenytoin, methotrexate) Vitamin B12 – lack of IF (post gastrectomy (uncommon))

↑ Breakdown → Haemolysis Haemoglobinopathies (SCD – seasonal joint pains, jaundice) Malaria(Enemic region)

2. Bleeding disorders

Congenital Family history of bleeding disorders e.g. haemophilia A or B, Von

Willebrand disease

Acquired Liver disease Drug history

a) Platelet aggregation inhibitors NSAIDs (stop 10 days prior to surgery)

b) Anticoagulants Warfarin (stop 3 days prior to surgery and check INR) Heparin (stop at least 6 hours prior to surgery)

3. Cardiorespiratory disorders

Some diseases are contraindicated in certain blood conservation methods: IHD Hypertension

NB: Severe hypertension predisposes to severe bleeding during surgery. Hence BP needs to be controlled before surgery

Peripheral vascular disease Renal impairment Thrombotic strokes

PHYSICAL EXAMINATION

1. General Examination

Pallor (and degree) Conjunctivae Tip of tongue Nail beds Sole of feet Palm

Jaundice Haemolytic anaemia or liver disease

Skin manifestations of bleeding disorders Petechial haemorrhage – minute haemorrhage on body surface Ecchymosis – extravasation of blood from ruptured blood vessels into subcutaneous tissue Haematomas – especially in joint spaces

2. Cardiorespiratory System - For any abnormality which will affect oxygen delivery

3. Abdomen

Hepatomegaly

Splenomegaly Haemoglobinopathies Haematological malignancy (Haematologist consult)

INVESTIGATION

* Blood tests should not be routine to ↓ blood loss

1. Baseline FBC, Sickling test, BUE & Cr, CRP, ferritin

Platelet count ≥ 100 x 109/L Hb: 7-8g/dl is acceptable in well compensated and otherwise healthy

individual presenting for minor surgery However higher preoperative Hb is indicated before elective surgery in

the following Anaemia – Signs of decompensation (eg. angina, dyspnoea) Blood loss – major surgery/ significant blood loss expected(>10ml/kg)

(due to ↓ oxygen carrying capacity of blood)

Co-existing significant cardio-respiratory disease It may limit ability to further compensate for reduction in oxygen supply due to operative blood loss, cardio-respiratory depressant effects of anaesthetic agents

2. Specific Blood film comment, LFTs, folic acid and B12 level Clotting profile for coagulation disorders

TREATMENT OR CORRECTION

1. Anaemia ↓ EPO (renal disease) → recombinant human EPO ↓ folate → folic acid ↓Iron → Iron supplements ± EPO Malarial → antimalarials Helminthic infestation e.g. hookworm→ deworming (Albendazole)

2. Bleeding Disorders Need haematologist consult

3. Cardio-respiratory Disorders Need physician consult

Human Recombinant Erythropoietin

EPO is a glycoprotein produced by the kidney in response to tissue hypoxia

Renal tubular cells Renal peritubular cells Mesangial cells

Originally used in the management of chronic anaemia due to renal failure or cancer chemotherapy

Currently plays a key role in blood conservation.Used to augment preoperative Hct ± intention of PABD or ANH

Route: IM/ SC/ IV (gives higher plasma levels)

Dose varies but iron supplementation required

Mechanism of action Causes committed stem cells to be converted to RBC lines Dose dependent increase in reticulocyte count, Hct and Hb

Adverse Effects More common in patients with renal insufficiency Hence unclear if adverse effects are due to renal disease/ EPO

therapy/ Both CNS – seizures, CVA, hypertensive encephalopathy CVS: MI, hypertension Others: hyperkalaemia, thrombosis

INTRAOPERATIVE STRATEGIES

PATIENT POSITIONING(POSTURE)

ANAESTHESIA TECHNIQUE

AUTOLOGOUS BLOOD DONATION

PHARMACOLOGIC AGENT

SURGICAL TECHNIQUE

PATIENT POSITIONING (POSTURE)

Before surgery starts the patient is usually positioned to meet the needs of the surgery in question

Good patient posturing helps with Comfortable Access to surgical site

Reduction in Blood loss Good/ Clear view of the body part to be operated on Minimizes Damage to the nerves through traction/ compression

MECHANISM/ EFFECT OF POSTURE ON BLOOD PRESSURE AND BLOOD FLOW

BP effect

↑ going below heart

↓ going above heart

± 0.77mmHg per centimetre of vertical distance at the density of normal blood

Blood volume

↑ with ↑ BP (arterial/ venous)

↓ with ↓ BP (arterial/ venous)

NB: because the veins are more compliant than arteries (i.e. cα δV/δP); a small change in pressure in venous system leads to significant accumulation of blood)

1mmHg pressure increase in circulatory system can lead to accumulation of blood in the venous system up to 8 times the volume in the arterial system

Both (net effect)

Gravity

↑ increases blood flow (due to↑ BP)

↓ venous drainage (due to congestion)

Combination of the two leads to ↑ blood loss

Level of the operative site should be a little above the level of the heart → This will lead to ↓ blood flow to the operative site and reduces venous congestion

Trendenlenburg position (head down)

most appropriate for abdominal, pelvic, lower limb procedures

Reverse Trendenlenburg position (head up)most appropriate for head and neck surgery

NB: in the head up position

Pressures in the veins above the level of the heart are subatmosphereic

Hence if a large vein above the level of the heart is opened to the atmosphere during surgery, there is potential of air to enter the circulation causing an air embolus

This complication is rare and can be avoided with careful surgery

ANAESTHESIA TECHNIQUE

SPINAL ANAESTHESIA – Systemic vasodilatation

GENERAL ANAESTHESIA

CONTROLLED HYPOTENSIVE ANAESTHESIA

GENERAL ANAESTHESIA Volume of blood at operative site depends on two main factors

Blood flow to surgical site (Q) Determinants

MAP – prevents episodes of hypertension and tachycardia due to sympathetic overactivity by causing adequate levels of anaesthesia and analgesia

Peripheral resistance – prevent widespread vasodilatation due to hypercarbia (CO2 retention) by controlling ventilation

(need for capnograph monitoring)

Venous drainage from site Impaired by

Cough (impair venous drainage) Straining Patient movement

Adequate muscle relaxation to prevent unnecessary manoeuvre

CONTROLLED HYPOTENSIVE ANAESTHESIA This is the deliberate reduction in the blood pressure to facilitate surgery

and it improves the surgical field and may reduce blood loss between 30-50%

Contraindications include HPT, IHD or Valvular Heart DX, RF, previous CVA.

Posture

Regional epidural / spinal

Volatile anaesthetics

Hypotensive agents

B-blockers: Labetolol 2-10mg bolus. Infusion –2.5-30ug/kg/min

Esmolol, 50-250ug/kg/min

Vasodilators

Hydrallazine, 2-5mg boluses

Na nitroprusside, 0.3 – 0.5ug/kg/min

GTN, 0.25 - 5ug/kg/min

Phentolamine 1-4mg boluses

AUTOLOGOUS BLOOD TRANSFUSION (ABT)

Definition Transfusion: reinfusion Blood: of Blood Autologous: which belongs to same patient (after initial collection)

Classification Acute Hypervolaemic Haemodilution Acute Normovolaemic Haemodilution Periopertaive Blood Salvage) PABD (Preoperative Autologous Blood Donation)

This is done in the preoperative period Not accepted by Jehovah’s Witness’

ACUTE NORMOVOLAEMIC HAEMODILUTION

Definition Acute (process is conducted relatively rapidly over minutes) Normovolaemic: blood volume of patient is maintained normal/ same Haemodilution: blood of patient is diluted with asanguinous fluid

infusion

Synonyms Acute isovolaemic haemodilution Acute normovolaemic anaemia Controlled normovolaemic exsanguination

Indication General

Anticipated blood loss >20% of circulating blood volume

(1000ml for 5L volume)

Specific Accident centre: Orthopaedic surgery: joint replacement

procedure Cardio: cardiac surgery/ vascular surgery (major reconstructive vascular surgery) Ground floor: Neurosurgery (major back procedures) 1st floor

GU: urologic surgery – nephrectomy; cystectomy; prostatectomy

General surgery – major bowel resection; cancer resection Eye: ↔ ENT: ↔ MFU: ↔

Contraindication

Anaemic Level

Initial Hct ≥ 36% (Hb ≥ 12g/dl)

(* values as low as 24% may be acceptable – Hb ≥8g/dl)

Blood coagulation disorders Because dilution of blood with asanguinous fluid also dilutes

coagulation factors eg. platelets Hence this will worsen underlying coagulation disorders

Coexisting disorder CNS – significant cerebrovascular disease : cannot tolerate lower Hct

value CVS – severe hypertension/ underlying cardiac disorder (severe aortic

stenosis/ unstable angina) : cannot tolerate lower Hct value, impaired ability to compensate for anaemia

Resp – severe pulmonary disease : impaired ability to compensate for anaemia

Infants < 6/12 Persistence/ presence of foetal Hb leads to leftward shift of oxyhaemoglobin dissociation curve which impairs oxygen release at tissue level to compensate for iatrogenic dilutional anaemia

ACUTE NORMOVOLAEMIC HAEMODILUTION

Can be performed in awake or anaesthetised patients Awake – prior to induction of anaemia

Adv: Abundance of time to perform procedure Ability to assess heamodynamic consequences in absence of any anaesthetic agent

Blood collection bags that contain anticoagulant are neededCitrate is used typically premixed with phosphate and dextrose (CPD)

Can be performed in awake or anaesthetised patients Awake – prior to induction of anaemia

Adv: Abundance of time to perform procedure Ability to assess heamodynamic consequences in absence of any anaesthetic agent

Blood collection bags that contain anticoagulant are needed

Citrate is used typically premixed with phosphate and dextrose (CPD)

Calculation of volume of blood to be collected

[Baseline (Hb/ Hct)] - [Average (Hb/ Hct)]

[Target (Hb/ Hct)]EBV x

EBV – Neonates → 85-95ml/kg body weight Children → 80ml//kg body weight Adults →70ml/kg body weight

Baseline Hb/ Hct – ideally ≥12g/dl or 36% Target Hb/Hct – 7-8gdl or 20-25% (below this level may precipitate dilutional coagulopathy of tissue hypoxia)

Average Hb/ Hct = baseline (Hb/ Hct) + target (Hb/Hct) 2

Eg. Adult male (weight 90kg baseline Hb 14g/dl)

Elect Target Hb = 10g/dlEBV = 90 x 75 = 6750mlAverage Hb = (14+10)/2 = 12Volume of blood to be collected = (14-10)/ (12 x 6750) = 2250mlNB: max no. of units of blood removed is 3

INTRAVENOUS ACCESSa) Arterial line

Adv: arterial pressure serves as a pressure head that pumps the blood into collection bag

Disadv: inability to do invasive blood pressure monitoring; to monitor beat to beat BP

b) Venous access Adv: invasive BP monitoring possible Disadv: blood sequestration is a passive process and its speed is

influenced by gravity

Types:

a) Central ( + large bore peripheral IV) – most reliable and effective because lack of venous valves to slow down flow and cause sludging; most popular sites are internal jugular and subclavian (but can be placed anywhere)

b) 2 large bore peripheral – most popular but has sludging risks; needs at least 18G cannula; 2 large cannulae are inserted in opposite arms to aid flow)

Emptying

Patient 3 way tap attached to cannula opened for blood to flow into tubin Blood should be seen flowing through tubing of collection bag Must ensure that blood doesn’t lump and coagulate in the tube

leading to flow obstruction Tubing shouldn’t be too long to minimize tubing dead space Flushing of tubing periodically with N/ Saline

Collection bag Add mixture of blood and CPD ‘anticoagulant’ as blood flows into

collection bag to prevent sludging/ clumping off RBCs or platelets.(automatic or manual)

Blood quantity – typically 450ml of whole blood is collected into each bag.

Subjective: experienced eye to adjudge whether collection bag is overfilled or underfllled

Objective: weighing (1ml of blood weighs 1g)

Advantage: to accurately calculate amount of asanguinous fluid is required to maintain normal blood volume for adequate volume resuscitation

Labelling

Patient info: Name; Age; Sex; Hospital number

Collectors info: Name; date and time of collection

Marked: UNTESTED BLOOD FOR AUTOLOGOUS USE

Storage

Room temperature (20°C) Must be re-infused (after haemostasis controlled) within 6hrs as haemolysis takes place after 6 hours at room temperature 1st unit salvaged is given last

Refrigerant (0°C) To be used if not going to be re-infused within 6hrs Must be re-infused within 24hrs Disadv: decease or inactivate platelet function

Fluid resuscitation

Occurs concurrently with blood sequestration

Types – Crystalloids and colloids

1)Crystalloid (isotonic fluids) – N/S and R/L

Advantages Easily diuresed (prevent fluid overload) Inexpensive (cost)

Disadvantages Entire fluid does not stay in intravascular space. [3:1

replacement ratio (3ml crystalloid: 1 ml blood loss)] → ↓ colloid osmotic pressure → Tissue oedema → May compromise oxygen delivery due to increased diffusion

distance from vascular space to cells

2)Colloids Advantages

Stay in intravascular space [1:1 replacement ratio] Less risk of tissue oedema

Disadvantages Expensive Not easily diuresed Most colloids have a half life longer than 4hrs and may not be rapidly diuresed

from body Therefore there is at least the theoretical risk of hypervolaemina and fluid

overload if the sequestered blood is re-infused rapidly after haemostasis has been achieved

Types Short acting [t1/2 < 4 hours] – Pentastarch; Dextran 40

Intermediate acting [t1/2 4-24hrs] – Dextran 70

Long acting [t1/2 >24 hrs] - albumin, high molecular weight HES e.g. Hetastarch (can have adverse effects on haemostsis when infused in volumes >20-25ml/kg)

MONITORING

Basic

ECG – continuous HR (gives idea of volume replacement + urine output), ST segment info (ischaemic changes)

Pulse oximeter – oxygen saturation

BP – invasive BP preferred as it gives beat to beat blood pressure

Capnography – adequacy of circulation

Additional

CVP (central venous pressure) – assess volume status and oxygen delivery

PAP (pulmonary arterial pressure)

Transoesophageal echocardiography – real time assessment of ventricular and valvular performance

Haemodynamic consideration Physiological response to anaemia

In future Combination of ANH and artificial oxygen carrier Technique known as ‘Augmented ANH’

Jehovah Witness consideration ‘closed circuit ANH’ Whole blood collection circuit and fluid resuscitation system have to

remain continuous with patient’s intravascular compartments Once blood collection in patient has been achieved it should be

allowed to trickle slowly back into patient to resemble venous flow

NB: If all the whole blood cannot be administered in the operating room, reinfusion can continue in the recovery room. However when patients emerge from anaesthesia they and their families need to be prepared that the whole blood is autologous and it is the end phase of the ANH technique

CLOSED CIRCUIT ANH

– Advantages

1. RBC (Hb) Fewer loss of RBC & Hb per given volume of blood loss E.g. A - Starting at Hb=14g/dl

blood loss volume = 1000ml

amount of Hb loss = 140g (1000ml → 14g)

B - Starting Hb 10g/dl (after ANH)

blood volume loss = 1000ml

amount of Hb loss = 100g (1000ml → 10g)

Difference between A & B = 40g of Hb

2. Platelets and coagulation factros Provision of fresh supply durng re-infusion

Problems/ Pitfalls/ Disadvantages

A. Anaemia/ haemodynamic change during blood collection period leads to ↓ BP and ↑ HR

B. Blood clumping in tubing and collection bag – slows collection process

C. Collection bag overfilled/ underfilled

D. Distraction – conduct of anaesthetist OR blood collection process OR both

E. Entering allogenic blood pool in blood bank

ACUTE HYPERVOLAEMIC HAEMODILUTION

Definition Acute (process is conducted relatively rapidly over minutes) Hypervolaemic: blood volume of patient is increased Haemodilution: blood of patient is diluted with asanguinous fluid

infusion

Pitfalls This technique is not as widespread as ANH and is relatively new There is not enough data about its use and safety

Indications and contraindications Similar to ANH

Calculation of amount of volume expansion required to achieve Hct of 20-25%

Subjective – 20-40ml/kg IV fluids fast

Objective (Kumar et al proposed equation)

Volume of fluid to be infused=EBV x Hi – HT x EF

EBV – estimated blood volumeHi – initial haematocritHT – target haematocrit (20-25%)

EF – expansion factor

• Definition: depends on ability of fluid used for haemodilution to expand plasma volume of

patient

• e.g. Fluid with volume effect of 80% (i.e. 80% of fluid stays in intravascular space) will have EF = 100/80 = 1.25

• Hence its is important to choose fluid that has an intravascular residence time similar to the

time of surgery. This is in order to maintain hypervolaemia during surgery.

Colloids are preferable – HES, dextran 40, gelatin

HT

PERIOPERATIVE BLOOD SALVAGE

Definition Process of

Collection + anticoagulation Filtration ± centrifugation and washing Reinfusion of shed blood into the same patient

Classification Timing of collection of blood

Intraoperative period Post operative period

Unprocessed blood (not washed)/ Processed blood (washed)

Benefits of washing blood – discussed later

Indication General

Anticipated blood loss >20% of circulating blood volume Current blood loss is significant to require blood transfusion Blood type transfusion rare and adequate amounts of allogenic

blood cannot be found

Specific Elective cardiothoracic procedures Emergencies

Ruptured ectopic gestation Ruptured spleen

Contraindication

A. Amniotic fluid contamination - (seen in pregnant women). It initiates intravascular coagulation

B. Bacteria contamination – due to bowel contents/ infected wounds/ urine

C. Cancer surgery (controversial) Theoretical risk of dissemination of tumour cells because

standard filtration and washing does not remove malignant cells Risk is decreased by

Using specific filters (leucocyte depletion filter) Irradiation of salvaged blood to inactivate cancer cells

NB: There as been no established difference in prognosis in oncology cases between patients who had blood salvaged and those that did not.

D. Debris contamination (cells/ haemostatic agents protamine and thrombin]) – may initiate intravascular coagulation

E. Erythrocyte destruction (Haemolysis) – shed blood of more than 6hrs should NOT be re-infused since haemolysis of RBCs s likely to be complete

F. Fat contamination

This is often seen in orthopaedic surgery due to the marrow fat in wound blood

This is associated with fat embolism and related pulmonary endothelial damage

NB: even after filtration and washing or salvaged RBCs a s significant amount of fat remains in blood

*SCD is not contraindication for blood salvage

Sickle cells occur when Hb is deoxygenated. However in cell salvage blood id in contact with air and therefore Hb is oxygenated

Anticoagulants(why) blood collected from operation site comes into contact with tissue

factors leading to activation of clotting cascade with FDPs formed; leading to reduced levels of fibrinogen in salvaged blood

(≈ 1g/L) Hence Salvaged blood is unlikely to clot and block tubing of

conservation device. However if bleeding is brisk e.g. great vessels bleeding, there wont be enough time for blood to be exposed to tissue factors

Need to use anticoagulant regardless of rate of blood loss to be on a safer side

Anticoagulants(Types)

Heparin – avoid in patents with platelet dysfunction or heparin induced thrombocytopaenia (HIT)

CPD (citrate-phosphate-dextrose) Citrate – chelates calcium

Adv: improves platelet function Disadv: hypocalcaemia in hepatic insufficiency

Dextrose – used as a substrate for RBC glycolysis by-product of glycolysis is 2,3-diphosphoglycerate (DPG) 2,3-DPG regulates oxyhaemoglobin affinity by interposing itself between β-globin

chains of Hb molecule When β-globin chains are farther apart Hb oxygen affinity decreases leading to

increased oxygen release When β-globin chains are closer together Hb affinity increases leading to

decreases oxygen release NB: it takes about 18-36 hours for [2,3-DPG] in banked blood to return to normal

levels. During this period oxygen release to tissues is NOT effective

3 devices (based on method of blood collection)

Manual collection devices

Simple suction collection devices

Automated suction collection systems

Manual collection devices Collection: surgeon uses sterile ladle or small bowl to collect blood

from body cavity and transfer it into a larger bowl or kidney dish

Anticoagulation: anticoagulant solution from sterile bottle is added

Filtration: (Blood and anticoagulant) are filtered through4-6 layers of sterile gauze placed in a funnel into receiver

Reinfusion: the ‘receiver’ (sterile bottle containing the blood) is sealed with a stopper and re-infused into the patient using a blood transfusion set

MANUAL COLLECTION DEVICES

Simple suction collection devices Collection – simple suction machine creates a negative pressure

vacuum in canister to produce a pressure gradient between the canister and body cavity (source of blood). This causes blood to flow towards canister.

NB: maximum suction pressure should be 100mmHg (negative pressure) because higher suction pressure cause excessive haemolysis of RBC

Anticoagulant – It is added manually via port on canister (reservoir)

Filtration – blood and anticoagulant filtered through a micro filter (20-150µm) to remove large particles and cellular debris from blood, into a rigid reservoir with a disposable liner or collection bag

± washing: blood washing device

Reinfusion: processed or unprocessed using standard blood transfusion set

SIMPLE SUCTION COLLECTION DEVICES

Simple suction collection devices

BLOOD WASHING DEVICE

Automated suction collection systems Collection: automated suction is a blood aspirator with a double

lumen

Anticoagulant One lumen: aspirates blood from surgical site or operative field Second lumen: it is an anticoagulation line so that anticoagulant

can be combined with aspirated blood at a controlled rate.

Filtration: anticoagulated blood is filtered into a disposable reservoir

Washing: filtered blood is then centrifuged – this separates denser RBCs from plasma and

dissolves solutes (WBC, platelets, anticoagulants, cellular debris, RBC free Hb and other contaminants)

washed with saline- This dilutes plasma and dissolves solute and discarded.

Reinfusion: the salvaged RBCs are then re-suspended in normal saline and transfused immediately or within 6 hours

AUTOMATED SUCTION COLLECTION SYSTEMS

complications

More likely to occur when using large volumes of unwashed blood

Advisable NOT to salvage more than 1500ml of unwashed blood

A. Air embolism

B. Breathlessness (pulmonary insufficiency)

C. Coagulopathy and calcium derangement

D. Disease (sepsis)

E. Electrolyte imbalance and acid-base disturbance

F. Fat embolism

G. GU – renal dysfunction

H. haemolysis

A. Air embolisma) Aetiology – reinfusion of blood done under pressure (rare

complication)

b) Effect – mortality

B. Pulmonary dysfunctiona) Aetilogy - debris/ fatty acid (toxic) – damage pulmonary vasculature

b) Effect – pulmonary oedema etc.

C. Coagulopathya) Aetiology

anticoagulant usage – heparin/citrate may be re-infused in large amounts if washing of salvaged RBCs is not done properly

washing technique – washing of large volumes of salvaged blood (>2L) can lead to loss of platelets and clotting factors into waste bag. Monitoring of clotting profile is indicated when large volumes of RBCs are salvaged

DIC (intracellular components of blood activate coagulation cascade)

b) Effect - bleeding

C. Calcium homeostasis altered

a) Aetiology Citrate overload (anticoagulan)

↑ entry – large volumes of blood salvaged (↑ amounts of CPD)

↓ exit – hepatic insufficiency – slow citrate metaboliism

b) Effect – chelates serum calcium lading to hypocalcaemia

D. Sepsis – occurs when there is contamination of disposable circuit

E. Electrolyte imbalance

a) Aetiology – dilutional due to re-suspension of salvaged RBCs in saline for transfusion

b) Effect – depends on electrolyte

E. Acid-base disturbance

a) Aetiology – re-suspension of salvaged RBCs in saline

b) Effect – hyperchloraemic acidoses

F. Fat embolism

Explained under contraindication

G. Renal dysfunction and Haemolysis

a) Aetiology – haemolysis due to:

High suction level

Aspiration causing excessive mixing of air with blood

b) Effect

Turbulence of air → shear stress n RBC membrane → destruction of RBCs → free Hb → excess free Hb (Hb ≥ 150mg/dl exceeds binding capacity of haptoglobin) → haemoglobinuria → ARF

NB: if adequate diuresis is maintained (until urine free of Hb) Hb can be excreted without renal duysfunction

Monitoring – bedside dipstick (positive for RBCs); microscopy (no RBC)

Damage/ Malfunction of auto-transfusion devices

If tubing from the reservoir bag to the cell saver analyser is inadvertently clamped, pressure builds up in the tubing and this will cause tubing to disconnect from analyser and spray blood throughout operating room

Such problems mandate the need for personnel involved in the use of cell saver devices to be educated and familiar with the equipment prior to operating the device

PREOPERATIVE AUTOLOGOUS BLOOD DONATION

Definition

D – donation

B – of blood

A – by a patient

P – in the elective preoperative period

and subsequently re-infused into the same patient if operative blood loss necessitates blood transfusion

Indication

Surgical blood loss likely to result in transfusion (≥ 20% circulating blood volume)

Contraindication

A. Anaemia – patient unsuitable if Hb ≤ 10g/dl or Hct ≤ 30%

B. Bacteraemia

C. Cardio-resp disorders – angina, aortic stenosis, respiratory failure

D. Disorders – SCD/ anticoagulant therapy/ uncontrolled hypertension/ IDDM

NB: Age and weight are no longer a restriction

Paediatric age group – do not donate more than 10% of blood volume

Weight < 50kg – do not donate more than 9ml/kg

Process

A. Awareness of patient : Benefits of procedure Risk of procedure (including possibility of homologous transfusion Consent form signed Minimum criteria for autologous BP at the time of each donation

B. Collection Onset: about 5 weeks prior to surgery Duration: in adults about 1 unit of blood (450ml) is collected weekly (7

days) but last unit is collected at least 5 days prior to surgery Reason – allows time for the Hct to increase and time for plasma

proteins to normalise intravascular volume prior to surgery Effect – 4-5 units of blood may be available for use by the date of

surgery

Drug (oral haematinics)

Iron ± EPO helps boost Hb

Problems

Postponed or cancelled surgery

2 options

Crossover technique – into homologous pool

Leapfrog technique – serial re-transfusion of stored blood starting with the oldest donated blood. Then fresh unit of blood donated later.

Fridge storage

Blood should be stored in a refrigerator at 4°C (up to 35 days) in a section of the refrigerator separate from the homologous blood pool

Blood should be clearly labelled with name, age, sex, hospital number, blood group, AUTOLOGOUS BLOOD INSCRIPTION.

GXM

ABO grouping is required for patient identification

Other tests on blood donated are mandatory if cross over s going to occur e.g. transfusion transmitted disease

48hrs prior to surgery, fresh blood sample of patients is taken to ensure ABO compatibility because of increased risk of procedural errors leading to incorrect identification

Haemotransfusion indication

This should be based on same criteria used for the transfusion of homologous blood and should not be merely given because it is available

This is because of the risks of incorrect identification and possible bacterial contamination with banked blood.

Advantages Decreases need for homologous blood and its problems Crossover effect - provided donor has met all the criteria for

homologous blood donation (↑ donor blood pool)

Disadvantages Administrative setup required – considerable planning and

organisation required Bacterial contamination of blood id possible Cost is higher than allogeneic blood transfusion Disability may lead to ineligibility to donate e.g. severe cardiac

disease Errors such as clerical/ procedural which may cause

incompatibility of blood

PHARMACOLOGIC AGENTS FOR BLOOD CONSERVATION

Definition: drugs used to help reduce operative blood loss

Classification Procoagulants – encourage clot formation

rVIIaDDVP

Antifibrinolytics – slows down clot dissolutionTranexamic acidAprotinin

COAGULATION CASCADE

TPA + fibrinogen

I. Recombinant Factor VIIa Definition: obtained via recombinant DNA technology Kinetics:

(route) → intravenously (IV) dose varies (20-40µg/kg over 3 minutes)

Dynamics:

Factor VII plays a key role in extrinsic pathway (requiring tissue

damage) by activating Factor X which then enters common

pathway of coagulation cascade

Effect:

Non-specific symptoms such as headaches, nausea, vomiting

II. Deamino-8-D-arginine vasopressin (DDAVP)/ Desmopressin Definition: synthetic analogue of arginine vasopressin (ADH)

D – deamino – demination of hemicysteine at position 1 (one) of ADH (AVP)

Adv: protects DAVP from peptidase degradation hence prolongs t1/2 to 55-60 minutes

D – arginine – this substitutes L arginine at position 8 (eight) of AVP

Adv: limits activity of DDAVP on V1 receptors found on smooth muscle

CVS – hypertension Resp – broncho-constriction GIT – cramps Uterus - cramps

Route: intravenously (IV), subcutaneously, intranasally (both equally effective as IV but plasma concentration peaks after 1 hour)

Bioavailability (dose): 0.15-0.3µg/kg intravenously over 15-30 minutes n morning of surgery

Rapid administration causes endothelial cells to release prostaglandin which causes systemic vasodilatation and hypotension

III. Epsilon Aminocaproic Acid (EACA) & Tranexamic Acid (TXA)

Definition They are γ-amino carboxylic acid analogue of lysine (γ-ACL)

Route: oral/ IV (preferred in perioperative period) Bioavailability (dose)

EACA – loading: 100-150mg/kg; maintenance dose 10-15mg/kg/hr

TXA – loading: 10mg/kg; maintenance 1mg/kg/hr

lower doses than EACA becaue 7-10x more potent

Excretion EACA: 90% is excreted in urine within 4-6hrs of administration TXA: 90% is excreted in urine within 24hrs of administration

Epsilon Aminocaproic Acid (EACA) & Tranexamic Acid (TXA)

Definition

They are γ-amino carboxylic acid analogue of lysine (γ-ACL)

Route: oral/ IV (preferred in perioperative period)

Bioavailability (dose)

EACA – loading: 100-150mg/kg; maintenance dose 10-15mg/kg/hr

TXA – loading: 10mg/kg; maintenance 1mg/kg/hr

lower doses than EACA becaue 7-10x more potent

Excretion

EACA: 90% is excreted in urine within 4-6hrs of administration

TXA: 90% is excreted in urine within 24hrs of administration

MECHANISM OF ACTION

Competitive inhibition – binds to fibrinogen (at lysine potion) and this prevents TPA from binding to fibrinogen. Hence TPA is degraded rapidly. This reduces rate of conversion of plasminogen to plasmin (fibrinolysis) to lyse clots

Non-competitive inhibition – directly inhibits plasmin at higher concentrations

Adverse effects

Increases perioperative thrombotic events

Nausea, vomiting, diarrhoea, hypotension (when administered rapidly IV)

Aprotinin

Naturally occurring Serine Protease Inhibitor (SPI) which was first isolated from bovine lung in 1930

Route: Intravenous

High dose ≈ 6 million KIU

Intermediate dose ≈ 2-6 million KIU

Low dose < 2 million KIU

NB: KIU – kallikrein inhibitory units

Distribution Rapidly redistributed into extracellular fluid → Rapid accumulation in renal tubular epithelium → Rapid lysosomal degradation → Hence need for continuous infusion to maintain adequate

plasma concentration

Mechanism of Action Decreased coagulation: inhibits plasma kallikrein →

inhbition of formation of Factor XIIa in intrinsic pathway Decreased fibrin formation: inhibits plasmin

Adverse effects Increased peri-operative thrombotic events Renal toxicity (due to rapid accumulation in renal tubule)s Allergic reaction

SURGICAL TECHNIQUE The training, experience and care of the surgeon performing the

procedure is the most crucial factor in reducing operative blood loss

It involves preoperative planning and appropriate intraoperative techniques

Preoperative planning Surgical team composition: an enlarged team helps reduce operating

time hence reduce operative blood loss Strategy of complex procedures e.g. urethroplasty: This helps patients

to recover haemodynamically between procedures to reduce need for transfusion

Appropriate surgical technique

Non-invasive procedures No blood loss e.g lithotripsy (sound waves to break up kidney

stones into smaller bits allowing it to pass out of the urinary tract without creating an incision or cut

Minimally invasive procedures Little blood loss e.g. laparoscopy (key hole surgery), endoscopy

Invasive procedures

Risk of major blood loss. Hence:

Use vasoconstrictors: reduce blood flow to surgical site → ↓ blood loss

Use of Tourniquet

Meticulous heamostasis: Sutures Devices: electrocautery, argon beam coagulator Microwave coagulating scalpel

POSTOPERATIVE MANAGEMENT Blood loss and hypovolaemia can still occur in postoperative period

Hence it is important to try and prevent it. But if it still occurs, detect it early and treat

Preventative measures Postoperative oxygen

Inadequate oxygenation is a common problem in the early postoperative period particularly following GA

This will be confounded by the effects of reduced HB level and hypovolaemia which occurs →

Leading to tissue hypoxia Hence it is important to give supplementary oxygen to all patients

recovering from GA and monitoring O2 saturations sing pulse oximeter

Vitals monitoring ECG – ST segment changes to indicate ischaemia Pulse & BP

Tachycardia could be due to hypovolaemia Need to regularly check wound and drains for bleeding/

haematoma Postoperative blood salvage can be done if wound drain is insitu

Hypertension could be due to pain This may aggravate bleeding and increase blood loss Hence need to provide sufficient analgesia throughout

perioperative period

Fluid balance Fluid input-output chart should be monitored to ensure

normovolaemia

Intervention

Secure haemostasis (early surgical re-exploration) This is indicated where significant blood loss continues to occur in

the postoperative period and there is no treatable disturbance of the coagulation status of the patient

Top-up Haematinics: this will optimise the erythropoietin response and

restore the Hb level to normal more rapidly

Blood transfusion Indication based on

Anaemia – postoperative Hb Baseline – general condition of patient (whether surgery of

inadequate tissue oxygenation) Coexisting cardio/resp disease Continued blood loss

FUTURE OF BLOODLESS MEDICINE AND SURGERY (BLOOD SUBSTITUTES/ OXYGEN THERAPEUTIC AGENTS )

Blood substitutes/ oxygen therapeutic agents

Definition: A blood substitute is a pharmacological agent that performs the typical functions of natural blood

Types of red cell substitutes:

• HBOC - Hemoglobin-based oxygen carriers

• PBOC - Perfluorocarbon-based oxygen carriers.

A. Haemoglobin based oxygen carriers

These are being developed to allow oxygen transport by free Hb.

Older oxygen therapeutic agents have existed since 1930s using lysed RBC; however although they demonstrated oxygen carrying properties they were nephrotoxic in nature. Other side effects were attributed to dissociation of the Hb tetramer into dimers and polymers

Currently 3 different substitues exist and are undergoing clinical trials

PolyHeme, which is a glutaraldehyde cross-linked human Hb;

Used in patients with severe injuries – led to reduction in overall 30-day mortality and reduction in allogenic blood use overall as well as a reported reduction in incidence of multi-organ failure

Hemolink (o-raffinose polymerized Hb);

Prepared from is prepared from outdated human RBCs. The cells are washed to remove plasma proteins and lysed (gently) filtered and pasteurised and finally purified using chromatography

Added to ringers lactate to produce product with Hb concentration 10g/dl

Has been trialled in patients undergoing coronary artery bypass graft in conjunction with ANH.

Overall patients had increased transfusion avoidance and reduction in units of allogenic blood transfused

Hemopure, which is a glutaraldehyde cross-linked bovine Hb

Lower oxygen affinity compared to Human Hb so facilitates easier oxygen unloading in tissue

Does not require refrigeration and is stable at room temperature for 2 years

Clinical trials have demonstratd reduction in transfusion requirements

Recent development of newer tetrameric rHb that do not cause vasoconstriction when infused and have fewer side effects eg. Hemozye, MP4 ( a tetramer combined with polyethylene glycol to create larger molecule to stay in intravascular space)

Perfluorocarbon-based oxygen carriers e.g. Fluosol 20

Definition carbon fluorine compounds characterized by a

high gas dissolving capacity (oxygen and carbon dioxide) low viscosity and chemical and biological inertness.

Unlike haemoglobin with sigmoid shaped dissociation curve, there is a liner relationship between oxygen partial pressure and oxygen content

Must be given with supplemental oxygen to maintain relatively high arterial oxygen partial pressures, which are necessary to maximize the oxygen transport capacity of fluorocarbon emulsions.

Intravascular perfluorocarbon solutions loaded with oxygen at a PaO2 of 200 mmHg can deliver 5 vol% of oxygen per decilitre of perfluorocarbon

Perfluorocarbons release 80% of their carried oxygen so can deliver approximately four times the oxygen that would be delivered by the same volume of Hb.

Giving 120 ml of Oxygent to a 70-kg patient is equivalent to 500 ml transfusion of whole blood

CHARACTERISTICS OF MAJOR OXYGEN THERAPEUTICS

CONCLUSION Patients should be given the option of choosing autologous blood

transfusion

They have the choice of PABD, ANH or soon Blood salvage

ANH provides warm, platelets and Factor VIII rich blood

Combination of PABD and ANH is possible

It is relatively easy to perform and reasonably safe

Erythropoietin is an accepted therapy for the increase in the Hb for autologous blood transfusion

EPO is worth its price when one thinks about HIV and this is accepted among Jehovah's witnesses

Properly planned rare blood groups can be easily done

Other blood conservation methods must be employed before thinking about allogenic blood

A patient who needs just a unit of blood probably does not need it

REFERENCES

1. Cardiovascular Physiology Concepts – Myocardial oxygen extraction: www.cvphysiology.com/CAD/CAD008.htm (Richard E Klabunde PhD)

2. Review of physiologic mechanism I response to anaemia: Paul C Herbert (MD, FRCPC, mHSc), Ling Qun Hu, George Bird

3. Acute normovolaemic anaemia: Physiological and practical concerns: P. Van der Linden (Dept. of Anaesthesiology, CHU Brugmann, Brussels, Belgium)

4. Anaemia and red blood cell transfusion in the critically ill patient: S.A. McLellan, D.B.L. McClelland, T.S. Walsh

5. Network for advancement of Transfusion alternative (NATA)

6. Oxygen delivery and consumption: Ilene M. Roben MD, Scott Manaker MD

7. Critical care medicine tutorials (oxygen)

8. Oxygen delivery: Nathan W Peterson, Lisa Moses

9. Acute Normovolaemic Haemodilution: Larry Eitel

10. Role of the red blood cell in Nitric oxide homeostasis and hypoxic vasodilatation: Mark T Gladwin

11. Peri-operative anaemia management: consensus statement on the role of intravenous iron

12. www.nba.gov.au/guideline/module2

13. medicine for residents- Iron and iron deficiency anaemia- quick recap

14. A Physician’s Guide to oral iron supplements (www.anemia.org)

15. Perooperative blood conservation www.schulich.vwo.ca/anaesthesia/perioperative-blood-conservation

16. WHO – clinical use of blood pdf

17. Iron metabolism – wikipedia

18. Oxygen content of blood: Anaesthesia UK (www.frca.co.uk/article)

28. Techniques of reducing perioperative blood loss by G. Inghitter

29. Cell salvage as part of a blood conservation strategy in anaesthesia (bja.oxfordjournals.org)

30. ANH policy in surgical patients

31. Global Blood safety Initiative (autologous transfusion in developing countries)

32. Transfusion alternatives for Jehovah’s Witnesses (St George’s Healthcare)

33. Cardiovascular pharmacology concepts – vasopressin analogues

ACKNOWLEDGEMENT

THANK YOU