Massive Blood Loss, Massive Blood Transfusion & Blood Conservation Strategies

1. Definition of Massive Blood Loss

• Loss of the total blood volume (TBV) within 24 hours — approximately 10 units of packed red blood cells (pRBC) in a 70 kg adult (since a 70 kg adult has ~5 L total blood volume, roughly 7% of ideal body weight).
• OR loss of 50% of total blood volume over a 3-hour period.

"Loss of total blood volume (10 units in a 70-kg adult) in 24 hr or loss of 50% of total blood volume over a 3-hr period." — Roberts and Hedges' Clinical Procedures in Emergency Medicine

2. Definition of Massive Blood Transfusion (MBT)

• ≥1 circulating patient blood volume within 24 hours (the most widely accepted definition), OR
• ≥10 units of pRBCs within 24 hours in an average-sized adult.

"A common definition for massive transfusion is the transfusion of at least one circulating patient blood volume within 24 hours. An approximate alternative definition for an average-sized adult patient may be the transfusion of 10 or more pRBC units within 24 hours." — Tietz Textbook of Laboratory Medicine, 7e

Massive Transfusion Protocol (MTP)

• 6 units pRBC + 6 units plasma + 1 apheresis platelet unit (reflecting a 1:1:1 ratio)
• Some evidence supports a 1:1:2 strategy favoring pRBCs in specific populations
• FFP/pRBC ratio of 1:1 may be most beneficial in exsanguinating hemorrhage
• Cryoprecipitate is added if fibrinogen remains <1 g/dL after FFP

• Dilutional coagulopathy (clotting factors fall to 25% activity after ~200% blood loss)
• Dilutional thrombocytopenia
• Hypocalcaemia (citrate toxicity)
• Metabolic alkalosis
• Hypothermia

3. Blood Conservation Strategies During Surgery

A. PREOPERATIVE STRATEGIES

B. INTRAOPERATIVE STRATEGIES

i. Acute Normovolemic Haemodilution (ANH)

• Remove 1–2 units of whole blood from the patient before systemic heparinisation/surgery; replace with crystalloid/colloid
• Blood is reinfused post-operatively, delivering fresh platelets and functional coagulation factors
• Caution in: preoperative anaemia, severe aortic stenosis, high-grade left main coronary disease, haemodynamically unstable patients

ii. Intraoperative Blood Salvage (Cell Saver)

• Shed blood is collected, washed, concentrated, and reinfused
• Can yield haematocrit up to 70% per processed unit
• Does not restore platelets or coagulation factors (washing removes them)
• Absolute contraindications: admixture with topical haemostatic agents, sterile water, alcohol, hydrogen peroxide, or povidone-iodine
• Use in malignancy/infection decided case-by-case

iii. Retrograde Autologous Priming (RAP) — Cardiac Surgery

• Patient's blood displaces crystalloid prime from the cardiopulmonary bypass (CPB) circuit into an external reservoir
• Reduces CPB-related haemodilution and extravascular lung water
• Hypotension may occur; treat with vasoconstrictors or Trendelenburg positioning

iv. Antifibrinolytic Agents

• Tranexamic acid (TXA): binds plasminogen, blocks fibrinogen lysis; reduces surgical bleeding and transfusion requirements without increased risk of PE, DVT, or MI
• Epsilon-aminocaproic acid (EACA): similar mechanism; used in cardiac surgery with/without CPB
• Aprotinin: was used but withdrawn after evidence of renal failure, MI, and death risk

v. Surgical Technique & Positioning

• Meticulous surgical haemostasis
• Optimal patient positioning to reduce venous engorgement (e.g., prone for spine surgery)
• Induced hypotension where appropriate

vi. Minimally Invasive Extracorporeal Circulation (MiECC)

• Shorter tubing and closed CPB circuits reduce priming volume and blood exposure, decreasing transfusion need in cardiac surgery

vii. Point-of-Care (POC) Coagulation Monitoring

• Thromboelastography (TEG) or Rotational Thromboelastometry (ROTEM) to guide targeted blood component therapy
• Avoids empirical, wasteful transfusions

C. TRANSFUSION THRESHOLD MANAGEMENT

• Restrictive transfusion strategy: Transfuse pRBCs only when Hb <7 g/dL; maintain Hb 7–9 g/dL
• In critically ill patients, restrictive strategy (Hb trigger <7 g/dL) is at least as beneficial as liberal strategy
• Exception: Acute coronary ischaemia — slightly higher Hb target may be appropriate
• Aim haematocrit ~30–35% to sustain haemostasis and oxygen delivery

D. PHARMACOLOGICAL ADJUNCTS

Summary: Four Pillars of Patient Blood Management

1. Preoperative optimisation of RBC mass — treat anaemia before surgery
2. Perioperative minimisation of RBC loss — optimise coagulation, use cell salvage
3. Interdisciplinary blood conservation — multimodal, team-based approach
4. Patient-centred decision-making — respect patient values (e.g., Jehovah's Witnesses)

Jehovah's Witnesses and Blood Transfusion — Clinical Management

Who Are Jehovah's Witnesses?

• Genesis 9:4 — "But you shall not eat flesh with its life, that is, its blood."
• Leviticus 17:10 — "If any one of the house of Israel eats any blood, I will cut him off from among his people."
• Acts 15:28–29 — "to keep abstaining from blood."

"Receipt of a blood transfusion is believed to cause irreversible death to a member's soul without hope of eternal life. Most Jehovah's Witnesses understand and accept the threat of death as a possible result of refusing therapeutic transfusion." — Barash, Cullen & Stoelting's Clinical Anaesthesia, 9e

What Blood Products Do They Refuse?

Absolutely Refused (by devout members):

• Whole blood
• Packed red blood cells (pRBCs)
• White blood cells (leucocytes)
• Platelets
• Plasma (including FFP)
• Stored autologous blood (preoperative autologous donation)

"Grey Area" — Personal Decision (varies by individual):

• Albumin — some accept
• Immunoglobulins — some accept
• Clotting factor concentrates (e.g., PCCs, Factor VIII/IX concentrates) — some accept
• Erythropoietin (EPO — contains albumin in formulation) — some accept
• Hemophiliac preparations — personal decision

Often Accepted (if blood remains in continuous circuit):

• Crystalloids (normal saline, Hartmann's, etc.)
• Colloids (hetastarch, dextran)
• Acute normovolemic haemodilution (ANH) — accepted by some if blood remains in continuous contact with the circulatory system (not stored)
• Intraoperative blood salvage (cell saver) — accepted by some if blood is in continuous circuit
• Cardiopulmonary bypass (CPB) — accepted by some for same reason

"Techniques of acute normovolemic hemodilution and intraoperative blood salvage have been accepted by some Witnesses, however, as long as their blood maintains continuity with their circulatory systems at all times." — Morgan & Mikhail's Clinical Anaesthesiology, 7e

Medical & Anaesthetic Management Strategies

Preoperative Optimisation

Intraoperative Strategies

Management of Life-Threatening Anaemia (Hb <5 g/dL)

• Optimise cardiac output (inotropes if needed)
• Maximise oxygen delivery: 100% FiO₂, PEEP, ventilatory optimisation
• Minimise oxygen consumption: sedation, hypothermia, muscle relaxation
• Hyperbaric oxygen therapy: can dissolve sufficient O₂ to sustain life without haemoglobin; used in pulsed fashion (3–4 hr/day) to reduce oxygen debt until Hb recovers
• Haemoglobin-based oxygen carriers (HBOCs): under investigation; not yet approved in the US but may revolutionise care for such patients

"Hyperbaric oxygen therapy can dissolve sufficient oxygen to sustain life in the absence of hemoglobin and may be another option when blood cannot be used." — Roberts & Hedges' Clinical Procedures in Emergency Medicine

Medicolegal Framework

Competent Adult

• A competent adult has the absolute legal right to refuse blood transfusion — even if the decision is considered unwise or life-threatening.
• They typically sign a waiver releasing medical practitioners from liability.
• Courts have ruled: "The competent adult has the right to refuse a transfusion regardless of whether his refusal arises from fear, religious belief, recalcitrance, or cost."
• However, this right is not absolute — courts may override refusal if it conflicts with state interests (preservation of life, prevention of suicide, protection of third parties).

Unconscious or Medically Incompetent Adult

• If the patient's beliefs are unknown in an emergency → transfuse (implied consent under the emergency doctrine; family members cannot refuse on their behalf).
• If beliefs are known in advance (e.g., patient carries a signed Jehovah's Witness card or advance directive) → courts tend to respect this objective evidence of patient intent.
• Advance directives and signed cards are legally recognised expressions of autonomy.

Minors

• Courts consistently override parental refusal of blood for children.
• The state's interest in preserving the life of a minor takes precedence.
• An urgent court order or temporary guardianship should be sought immediately.
• In genuine emergencies, physicians are legally protected in transfusing a minor to save their life.

Practical Steps for Clinicians

1. Engage early — for elective surgery, establish the patient's individual beliefs; do not assume all Witnesses hold the same position.
2. Document thoroughly — record all discussions, patient capacity, decisions made, and consent/refusal.
3. Contact the Hospital Ethics Committee and legal advisors if any uncertainty exists.
4. Over 1,700 Hospital Liaison Committees exist worldwide through the Jehovah's Witnesses organisation — these can assist with personalised healthcare management plans.
5. Seek an urgent court order for minors or unconscious patients without capacity.

"The best management for Jehovah's Witnesses is to have a well-prescribed perioperative care plan to maximise blood conservation strategies and a clear conversation about the patient's individual concerns and beliefs." — Barash, Cullen & Stoelting's Clinical Anaesthesia, 9e

Brain Death and the Apnoea Test

Definition of Brain Death

"Brain death occurs when there is an absence of signs of brainstem function or motor response to deep central pain in the absence of pharmacologic or systemic medical conditions that could impair brain function." — Schwartz's Principles of Surgery, 11e

• Severe traumatic brain injury (TBI)
• Aneurysmal subarachnoid haemorrhage (aSAH)
• Massive intraparenchymal haemorrhage
• Hypoxic-ischaemic brain injury (less common)

Prerequisites Before Brain Death Evaluation

"Brain death should not be determined within hours of emergency department evaluation or transfer from an outside facility" — Bradley & Daroff's Neurology, 7e

Clinical Examination — Brainstem Reflexes

1. Pupillary Response

• Pupils typically 4–7 mm (mid-dilated), non-reactive to bright light bilaterally
• Constricted (pinpoint) pupils are NOT compatible with brain death — raise suspicion of opioid effect

2. Corneal Reflex

• Absent bilaterally — tested with saline jet and tissue touch

3. Oculocephalic Reflex (Doll's Eye)

• Tested only if C-spine integrity is ensured
• Eyes remain fixed ("doll's eye" movement absent)

4. Oculovestibular Reflex (Ice-Water Calorics)

• Head elevated to 30° (horizontal canal becomes vertical)
• 50 mL ice water irrigated into each ear — observe for 1 minute, with 5 minutes between each side
• In brain death: no eye movement
• In comatose non-brain-dead patient: eyes deviate toward the cold side

5. Facial Response to Noxious Stimuli

• No grimacing to: supraorbital notch pressure, temporomandibular joint compression

6. Gag Reflex

• Absent — tested by stimulating posterior oropharynx (gloved finger)

7. Cough Reflex

• Absent — suction catheter passed to carina, no cough (minimum 2 passes)

8. Motor Response to Deep Pain

• No motor response to deep central pain: supraclavicular pinch, sternal rub, fingernail beds
• Decerebrate or decorticate posturing not compatible with brain death
• Spinal reflexes (e.g., triple flexion of lower limbs) — spinally mediated, compatible with brain death

Findings NOT Compatible with Brain Death (Box 6.2)

• Nystagmus or spontaneous eye movements
• Conjugate eye deviation
• Pinpoint pupils
• Grimacing to noxious stimulation
• Decerebrate or decorticate posturing

The Apnoea Test

Step-by-Step Protocol (Apnoeic Oxygenation-Diffusion Technique)

Positive Apnoea Test (confirms brain death):

• No respiratory effort, AND
• PaCO₂ ≥ 60 mmHg, OR rise of ≥ 20 mmHg above normal baseline

Time of Death:

Aborting the Apnoea Test:

Number of Examinations Required

Confirmatory Ancillary Tests

"The clinical examination and the excluding of confounders remains the foundation of brain death determination." — Bradley & Daroff's Neurology in Clinical Practice, 7e

After Declaration of Brain Death

• Family is informed that the patient has died but remains supported on artificial means
• After adequate time, family is approached regarding organ donation
• US federal law requires the physician to contact an organ procurement organization (OPO)
• Members of the OPO approach the family separately from the medical team

Brain Death and the Apnoea Test

From Anaesthesia & ICU Perspectives

Definition of Brain Death

"Brain death is declared when the clinical picture is consistent with irreversible cessation of all brain functions. Legal and medical brain death criteria differ from state to state, but all require permanent absence of both cerebral and brainstem functions." — Barash, Cullen & Stoelting's Clinical Anaesthesia, 9e

"The diagnosis of brain death remains one of the most challenging and controversial areas of neurocritical care. Physicians must have adequate training and understanding of the principles of brain death declaration and be able to apply them assiduously and without compromise." — Miller's Anesthesia, 10e

Prerequisites Before Brain Death Examination

"Potential reversible causes of coma such as hypothermia, hypotension, hypoglycemia, drug or toxin intoxications, and acid-base or electrolyte imbalances must be corrected prior to declaration of brain death." — Barash, Cullen & Stoelting's Clinical Anaesthesia, 9e

Clinical Examination — Brainstem Reflexes

• Unresponsive to all sensory stimuli
• Have no brainstem reflexes
• Have no ventilatory drive (confirmed by apnoea testing)
• May have complex motor activity originating from the spinal cord or peripheral nerves — this does NOT exclude brain death

The following must ALL be absent:

The Apnoea Test

"One of the tests should include an appropriately conducted apnea trial in the presence of the responsible physician, with confirmation of adequate changes in PaCO₂." — Miller's Anesthesia, 10e

Step-by-Step Protocol

Positive Test (confirms brain death):

• No respiratory efforts, AND
• PaCO₂ ≥ 60 mmHg, OR ≥ 20 mmHg rise from normal baseline

Aborting the Test:

"Four-vessel CBF angiograms are the 'gold standard' and are usually required to diagnose brain death during barbiturate coma or if a confirmatory apnea test cannot be performed." — Miller's Anesthesia, 10e

Confirmatory Ancillary Tests

"If the clinical criteria are incomplete, then ancillary testing such as cerebral angiography, transcranial Doppler, and/or electroencephalography can be obtained to confirm the clinical examination." — Barash, Cullen & Stoelting's Clinical Anaesthesia, 9e

Pathophysiological Changes After Brain Death (ICU Perspective)

Phase 1 — Catecholamine Storm (Sympathetic Surge)

• Intense vasoconstriction → hypertensive crisis (80–90%)
• Tachycardia
• Redistribution of blood volume → visceral ischaemia
• Acute myocardial injury — echocardiographic dysfunction seen in 40% of potential heart donors

Phase 2 — Autonomic Collapse (Brainstem Death / Herniation)

• Loss of sympathetic tone → vasodilation, vasoplegia
• Profound hypotension (80–90%)
• Reduced cardiac output
• Hypovolemia (capillary leakage, osmotherapy for ICP, diabetes insipidus)

Table: Pathophysiologic Changes with Brain Death (Miller's Anesthesia 10e)

Endocrine Disturbances:

• Central DI (loss of posterior pituitary) → severe fluid and electrolyte derangements (up to 90%)
• Anterior pituitary failure → ↓ T3, T4, ACTH, TSH, GH
• Hypothalamic dysfunction → loss of temperature regulation (hypothermia follows initial hyperthermia)

Respiratory:

• ↑ SVR → blood shifts to pulmonary circulation → pulmonary capillary leakage → neurogenic pulmonary oedema
• Proinflammatory cytokine release at alveoli → early graft failure risk in lung donors
• Without ventilatory support → apnoea → cardiac arrest

ICU Management of the Brain-Dead Organ Donor (Barash's Clinical Anaesthesia 9e)

• Dopamine — traditional first-line
• Vasopressin — preferred alternative; reduces pressor requirements, protects lung function, improves organ procurement rates
• Norepinephrine/phenylephrine — reserved for severe shock (high-dose catecholamines are detrimental to organs)

• Vasopressin/DDAVP — for DI and haemodynamic stabilisation
• T3 (triiodothyronine) — 4 µg IV bolus then 3 µg/hr infusion; recommended for cardiac donors with EF <45%
• Methylprednisolone — reduces systemic inflammatory response

• Lung-protective strategy: tidal volume 6–8 mL/kg, PEEP adjusted to minimise FiO₂
• For lung donors: maintain low CVP (diuretics before lung procurement)
• For kidney donors: higher filling pressures preferred

• Brain-dead patients may have intact spinal reflexes → NMB required during organ procurement to prevent movement