1. Bloodless Surgery and The Jehovah’s Witness Patient
Morbidity and Mortality Conference
Dr. Christopher Ray M.D. & Dr. Evan Pivalizza M.D.

2. Case Presentation #1
 Mrs. HM was a 51 year-old Jehovah’s Witness patient who was involved in a MVC with a large dump truck on The patient’s car was T-boned during the accident.
 She was life-flighted to HH as a code III and arrived in the ER with a GCS of 15
 She indicated in the ER that she did not want any blood even if it resulted in her own death.

3. Injures discovered included:
 Grade IV liver laceration  Large splenic laceration  Multiple open head lacerations  3 rib fractures  Pulmonary contusions
 The patient subsequently deteriorated in the ER and was emergently intubated with 22mg Etomidate and 120mg of Sux. for signs of shock.
 ER stated that the pulse ox would not picked up.
 The remainder of the patient’s PMH was noted to be negative.

4. Anesthesia Pre-op

5. Anesthesia OR Record

6. Anesthesia OR Record

7. Anesthesia Post-op

8. Post-op Events
 Patient taken to STICU with unstable VS  She was declared DNR by the surgeon  The patient later developed bradycardia and subsequent cardiopulmonary arrest. No CPR was performed and she was pronounced dead at 5:14pm
 Cause of death was not stated but appears to have been cardiac arrest as a result of severe internal hemorrhage.

9. Treatments Used
Cell Saver Hextend Albumin Lactated Ringer’s 4000 Aprotinin inf. Tham inf. Epinephrine inf. (low dose) Hypothermia (Unintentional)

10. Jehovah’s Witness
 This religion was founded in 1872 by Charles Russell in Pittsburgh, Pennsylvania. He later introduced The Watch Tower.
 Name changed to Jehovah’s Witness in 1931
 Witness’s officially adopted the policies of no blood transfusions in 1945 as a church decision.
Bible chapters that reference their beliefs include:  Genesis 9:3-4  Leviticus 17:  Acts 15:19-21

11. Leviticus 17:10-12
10 " 'Any Israelite or any alien living among them who eats any blood-I will set my face against that person who eats blood and will cut him off from his people. 11 For the life of a creature is in the blood, and I have given it to you to make atonement for yourselves on the altar; it is the blood that makes atonement for one's life. 12 Therefore I say to the Israelites, "None of you may eat blood, nor may an alien living among you eat blood."

12. Interpretation by Believers
 The JW religion and patient believes that by receiving blood products they will be cut off from having everlasting life after their death.

13. Ethical Issues
Competent Adult: Has the legal right to self-determination.
Incompetent Adult (emergency): Need a court direct BT
Minor (emergency): Need a court direct BT
Minor (elective): Need a court direct BT

14. Hermann Hosp. Procedure
Pediatric patient (<18 years old) with parents acting on the child’s behalf. In need of a blood transfusion 
Pediatric Social Worker is contacted immediately 
SW contacts Child Protective Services 
CPS contacts a judge who grants temp. custody to CPS 
Blood Transfusion(s) then takes place 
Custody is then transferred back to parents after the transfusion(s).

15. Acceptability of Blood Products
Acceptable
Not Acceptable
Questionable
Crystalloids
Whole Blood
Albumin
Colloids
Red Cells
Immunoglobins
Gelatins (Europe)
Platelets
Vaccines
G-CSF (most)
White Cells
Coagulation Factors
Epo. (most)
Plasma (FFP)
Hemodilution
Cell Saver
Organ TRP
Gelatins such as Hemaccel and Gelofusine are most commonly used in the UK and Europe but are not commerically avalible in the US. Composition NA=145 Cl=145 K=5 Acetate=6 Oncotic pressure=35-39

16. What JW Patient’s Desire
Treatment without the use of any blood products.
If any autologous blood is used it must stay in continuity with the body.
Many of these patients are willing to die rather than receive blood.
Patient’s request that alternative treatments be used.
This group of patients continue to pose ethical and clinical challenges for surgeons and anesthesiologist.

17. Anesthesia for Elective Surgery
Cardiac and vascular surgery have  mortality.
Other high risk procedures/conditions include:  repeat cardiac surgery  severe LV dysfunction  HCT <24 on post-op day 1
Acute BL > 500ml in anemic patient’s have  mortality
Pre-op Hct < 18% have an  mortality, irrespective of BL

18. Outpatient Elective Surgery
Preoperative Management
Treatment should be organized by the patient’s surgeon, anesthesiologist, and hematologist.
1. Erythropoietin
Glycosylated polypeptide released by the kidney in response to hypoxia. It increases erythropoietic precursors in the bone marrow.
Recombinant product made from Chinese hamster ovarian cell line.

19. Erythropoietin Dosing
600U/kg per week SC for 3 week on days (21, 14, 7, and day of surgery)
Alternatively the patient can get: 300U/kg per day SC for 10 days before surgery and 4 days after surgery
While treating the patient with Epo. simultaneous treatment with: 1. Iron 6mg/kg/day 2. B Folate

20. Erythropoietin
Complications/Side Effects include: 1. Seizures 2. Hypertension 3. Hyperviscosity
A study in ’93 by Viele & Weiskopf found that of 61 JW patients with a Hgb <8 and their cause of death was noted to be anemia the patient’s Hgb was less than 5.

21. Darbepoetin Alfa (Aranesp)
Novel Erythropoiesis-Stimulating Protein (NESP)
 Similar to Epo. but has a slight modification.  Half-life is 3 times longer with greater potency  Can be administered less frequently
 Approved in 2001 for Renal Failure and 2002 for anemia  Research currently underway for surgical use

22. Intraoperative Strategies
1. Acute Normovolemic Hemodilution
 Acute normovolemic hemodilution is the process of removing one or more units of blood at the beginning of surgery (prior to surgical incision) for transfusion to the patient either during or at the end of the operation.
 ANH reduces or eliminates the need for allogeneic blood, and is one of the least costly method of autologous blood procurement.
 ANH can be implemented during cardiac, major general, hepatic, neurologic, orthopedic, and urologic procedures.

23. Acute Normovolemic Hemodilution
 During ANH, whole blood is drawn from a patient prior to surgery, while restoring the circulating blood volume with acellular fluid.
 The collected blood is anticoagulated with a citrate based anticoagulant and stored in the operating room at room temperature to preserve platelet, clotting factor, and white blood cell function.
This procedure results in:   O2 carrying capacity   viscosity   SNS stimulation   VR, SV, CO   # of RBC’s lost during surgery

24. Volume Removed How Much Volume of Blood Can Be Drawn?
 ANH is usually limited to a volume of 2,000 mL or a target hematocrit (Hct) of 28%, which ever comes first.
V = EBV x (HI-HF)/HAV
Must remember that with a JW patient the blood must stay in continuity with the body.

25. Acute Normovolemic Hemodilution
Indications for Acute Normovolemic Hemodilution (ANH) 1. The anticipated intraoperative blood loss is 1 liter or more. 2. Any type of surgery associated with significant blood loss. 3. The desire for the patient not to receive previously donated autologous/donor blood products.  
Relative Contraindications for ANH 1. Anemia 2.  renal function & cannot excrete large amounts of fluid. 3. When an  in cardiac output is undesirable. (A.S., CAD) 4. Limitations of cardiac or pulmonary function

26. Acute Normovolemic Hemodilution
Cost Savings  Reduction in total transfusion costs ($100/unit with ANH) compared with ($269 with autologous).
Underutilized?  Time Consuming  Requires additional equipment/knowledge  The mean duration of hemodilution was 60.6 minutes, with 1 unit (500 mL’s) of blood removed every 17.8 minutes.
 Some studies suggest that significant (including economic) benefit only for redo hip surgery and radical prostatectomy

27. Intraoperative Strategies
2. Hypervolemic Hemodilution
 No blood is withdrawn  Blood volume is expanded aggressively  Decreased # of RBC’s lost during surgery  Postop diuresis and recovery
3. Regional anesthesia
 Epidurals performed for orthopedic procedures including Hip and Knee

28. Intraoperative Strategies
4. Controlled hypotension
MAP mmHG Do not use if the patient has CVS, CNS, Renal, or Liver dysfunction
5. Controlled Hypothermia
O2 consumption is decreased 6% for each C Increased O2 solubility in the plasma via a left shift of the oxyhemoglobin dissociation curve.
Must maintain temp > 33 C (arrhythmia, coag.)

30. Intraoperative Strategies
9. Aprotinin
 Aprotinin is a naturally occurring proteolytic enzyme inhibitor that was discovered in the 1930’s and launched in Germany as Trasylol in 1959.
 Trasylol is indicated for prophylactic use to reduce perioperative blood loss and the need for blood transfusion in patients undergoing cardiopulmonary bypass (CPB).
 Overall effect is antifibrinolytic and platelet protection

31. Aprotinin
PHARMACOLOGICAL ACTION: Trasylol forms reversible stoichiometric enzyme inhibitor-complexes with:  Human Trypsin  Plasmin  Plasma Kallikrien  Tissue Kallikrien  Elastase  Urokinase  Thrombin
Decrease Their Affinity

32. Aprotinin
 The effects of aprotinin results in a reduction in systemic inflammatory response, fibrinolysis, and thrombin generation, which translates into a decreased, need for allogeneic blood transfusions and reduced bleeding.
 By inhibiting pro-inflammatory cytokine release Aprotinin helps maintains glycoprotein homeostasis.
Platelets: reduces glycoprotein loss (e.g., GpIb/GpIIb/IIIa)
Granulocytes: prevents the expression of pro-inflammatory adhesive glycoproteins. (e.g., CD11b)

33. Aprotinin
Dose:  By slow intravenous infusion  Open heart surgery, loading dose is 2,000,000 units (200 mL) after induction of anesthesia and before sternotomy.  Maintenance dose, by intravenous infusion 500,000 units (50 mL) every hour until end of operation.
 Anaphylactic reactions are possible.
 Europe: wider applications to orthopedics, spine, and liver transplant procedures.

34. Intraoperative Strategies
10. Cell Saver
 Collected blood is citrated, filtered, washed with saline, concentrated, and returned to the patient.
 Frequently used when blood loss is expected to more than one liter
 Contamination by bacterial or malignant cells are relative contraindications.
 Remember with a JW patient to maintain continuity
Cost: $1600

35. Intraoperative Strategies
11. DDAVP (Desmopressin)
 A synthetic analogue of ADH (Vasopressin)
  Plasma levels of Factor VIII and vWF in deficient and healthy patients.   Platelet adhesion to the vessel wall. (No effect on platelet count or aggregation)   PTT and Bleeding Time
M.O.A.  Not completely understood
 Used for Hemophilia A, vWD, DI, and bed wetting

36. DDAVP  Medication if given IV or SC
 Dose of .3mcg/kg over 30 min. will help prevent tachycardia, flushing, tremors, or chest pain.
 Observe for signs of water retention and hyponatremia esp. if given with loop diuretics.
 Clinical studies show  bleeding after cardiac surgery in selected patient’s with platelet dysfunction.

37. Intraoperative Strategies
12. Artificial Oxygen Carries
 Artificial oxygen carries are grouped into hemoglobin-based O2 carriers and perflourocarbon emulsions. These drugs are still undergoing extensive clinical testing
 Flourocarbons
 In the June '03 of Anes. a study found the use of perfluron emulsion as a artificial oxygen carrier was shown to improve hepatocellular injury after hemorrhagic hypotension when compared to using blood, colloid, or combo of blood and colloid.

38. Flourocarbons
 In the Dec.'02 issue of Anes. a European phase II trial suggested that when perfluron emulsion was used in high blood loss non-cardiac surgery there was a decreased allogenic blood transfusion requirement. There were more adverse events in the PFC group 86% vs. 81% and more serious events 32% vs. 21%. Mortality was the same. (cardiac/digestive/nervous)

39. Intraoperative Strategies
13. Recombinant Factor VIIa (NovoSeven)
 Produced by baby hamster kidney cell lines and free of human protein.
 Is indicated for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII or Factor IX.
 There are 2 case reports in this month’s issue of Anes. that report on two patients who underwent MVR with the use of Aprotinin in the CPB. Both were treated with rFVIIa after bleeding was noted at the end of the case and had significant improvement within 3 and 8 minutes.

40. Novoseven
A study out of Europe by Levy et al. using a single dose of rFVIIa verses placebo in patient’s undergoing transabdominal prostatectomy found an reduction in blood loss from 2,450 to 1,400.

41. Novoseven
Recombinant FVIIa is a factor VIII and/or IX bypassing agent and initiates hemostasis through the tissue factor (TF) dependent coagulation pathway. 
When complexed with tissue factor:  Activates Factor X to Factor Xa  Activates Factor IX to Factor IXa  Factor Xa, with other factors, then converts prothrombin to thrombin, which leads to the conversion of fibrinogen to fibrin
 Consider a TEG

42. Review of Coagulation Cascade

43. Postoperative Strategies
1. Increase CaO2 (Arterial O2 content)
 As RBC vol.  the normal 2% of O2 that is dissolved in blood increases to as much as 25%   FiO2  Possible with Hyperbaric O2, but prolonged use would lead to toxicity.
CaO2 = SaO2 (Hgb x 1.34) + (PaO2 x )

44. Postoperative Strategies
2. Decrease CMRO2
 Sedation, Analgesia  PPV, muscle relaxation  controlled hypothermia
3. Minimize Phlebotomy

45. Tromethamine Tham
 A buffer that can be used to treat metabolic acidosis when concerns exist regarding CO2 accumulation from the metabolism of administered sodium bicarbonate.
 Tham is 0.3 M solution adjusted to a pH of approximately 8.6 with glacial acetic acid.
 Acts as a proton acceptor and corrects acidosis by binding hydrogen ions (H+) and increases in HCO3
 Cleared by the kidneys
Contraindicated: Tham Solution is contraindicated in anuria and uremia

46. Tham The following formula is a general guide:
(mL of 0.3 M) = Wt(kg) X Base Deficit (mEq/liter) X 1.1
For example a 100 kg pt. with a buffer base deficit (negative base excess) of 5 mEq/liter
would require 100 x 5 x 1.1 = 550 ml of Tham Solution

47. Case Report #2
 47 y/o JW patient with Hep. C, pancytopenia, and splenic lymphoma presented to HH as an outpatient for an elective splenectomy.
 Preoperatively he was severely anemic and was referred to the hematologist where he was started on 10,000 U/d SC Epo. for six weeks. Before his surgery his hgb was 5.3g/dL, PT 13.8, and PTT 41.5.
 Preoperatively the patient underwent splenic embolization by IR

48. Case #2 Intraoperatively
 Patient was given a loading dose of Aprotinin along with an infusion. Cell Saver and Albumin used for volume.
 Anes. was induced with STP, Fent., Roc/Panc. and maintained with Isoflurane (0.7%-1.2%)
 EBL was 500
 The surgery went uneventful and the patient was extubated within 15 hours and later discharged.