Bloodless Medicine Strategies

Hyperbaric oxygen therapy (HBO) is a medical treatment in which patients inhale 100% oxygen in a total body chamber, under increased but controlled pressures. It is used for a wide variety of treatments, usually as a part of an overall medical care plan. Under normal circumstances, oxygen is transported throughout the body by red blood cells. With HBO, oxygen is dissolved into the body’s plasma in significant concentrations, and can be carried to areas of the body where circulation is diminished.

HBO is an important and potentially life-saving strategy for patients for whom blood is not an option, because it greatly increases the oxygen content of plasma to a clinically significant level, independent of hemoglobin concentration. Since the hemoglobin in red blood cells normally carries most of the oxygen that sustains the life of cells, HBO is a safe and effective way to provide support for patients who are anemic or profoundly anemic. HBO is generally well tolerated by patients, and is safe when administered by trained medical staff in a hospital setting.

FEATURED MEDSTAR EXPERT

Dr. Kelly Johnson-Arbor, reports on the application of bloodless strategies to adult care:

Hyperbaric Oxygen Therapy in Bloodless Medicine and Surgery

Red blood cells contain hemoglobin; hemoglobin is the major carrier of oxygen throughout the human body. When hemoglobin levels decrease, anemia results and patients may exhibit signs and symptoms of decreased oxygen delivery to tissues (also known as oxygen debt). The signs and symptoms of oxygen debt may include tachycardia, dyspnea, fatigue, chest pain, and altered mental status; laboratory findings may include metabolic acidosis, hyperlactatemia, and elevated cardiac enzymes. Transfusion of packed red blood cells is generally administered to anemic patients who are symptomatic, with the goal of relieving their signs and symptoms of oxygen debt.

The amount of oxygen delivered to the body (DO2) is dependent on the arterial oxygen content (CaO2) and cardiac index (CI).1 The equation representing this is as follows:

DO2= CaO2 x CI

The CaO2 is mostly dependent on hemoglobin concentration; each hemoglobin molecule can carry up to 1.38 ml of oxygen per gram of hemoglobin.1 A very small amount of the arterial oxygen supply is dissolved in the plasma and is dependent on the partial pressure of oxygen in the blood (PaO2). The CaO2 is determined by the following equation:

CaO2= (Hemoglobin [g/dL] x 1.38 ml O2 x %oxygen saturation) + (0.003 x PaO2)

Oxygen that is delivered to tissues is then extracted and used by the tissues. On average, the human body extracts 5-6 vol% of oxygen from the blood.1 As long as oxygen supply equals or exceeds the amount of extracted oxygen, symptoms of oxygen debt do not occur. In anemic patients, oxygen delivery via hemoglobin may not be sufficient to compensate for oxygen extraction. When hemoglobin concentrations drop below 6 g/dL, oxygen delivery and extraction become unequal, and when hemoglobin concentrations drop below 4 g/dL, tissue oxygenation delivery is significantly impaired.2 At hemoglobin concentrations less than 6 g/dL, impairments in memory and reaction time occur in humans.3

Historically, indications for transfusion of red blood cells were based on hemoglobin concentrations. Prior to the 1980’s, the “10/30” rule was a commonly followed transfusion protocol; according to this rule, a patient’s hemoglobin and hematocrit should exceed 10 g/dL or 30%, respectively, prior to operative procedures.4 Modern recommendations for management of anemia include transfusion thresholds that are based on both laboratory values and patient-specific factors.5 Currently, a commonly utilized threshold for transfusion of packed red blood cells is a hemoglobin concentration of 7 g/dL in patients who exhibit signs or symptoms of anemia. This threshold is based on the disequilibrium of oxygen delivery and extraction as well as the clinical symptoms that occur at higher frequency below this hemoglobin concentration.

Blood transfusions are common in hospitalized patients; in 2013, over 13 million blood products were transfused to patients in the United States.6 Some patients, however, are unable to receive blood transfusions due to religious beliefs or other reasons. According to the Jehovah’s Witnesses religion, portions of the bible (including Genesis 9:4, Leviticus 17:12, Deuteronomy 12:23, and Acts 15:29) state that its followers must abstain from receiving blood.7 Jehovah’s Witnesses will not accept blood transfusions, and this religious belief has been upheld in the American legal system. Some patients are unable to accept blood products due to medical reasons. Examples of this include patients with hemolysis and antibody formation due to transfusion reactions, or those with crossmatch incompatibility. Patients who cannot accept blood transfusions for medical or religious purposes are at increased risk for morbidity and death after acute and unexpected blood loss from conditions including postpartum bleeding, trauma, and intraoperative hemorrhage.2 Many hospitals have established bloodless medicine programs which focus the diagnosis and treatment of anemia and the minimization of blood loss in the population of patients who cannot accept transfusions.8 Strategies included in bloodless medicine programs may include administration of iron and erythropoietin, use of pediatric phlebotomy tubes to limit iatrogenic blood loss, minimization of unnecessary blood draws, and administration of hyperbaric oxygen therapy.

Hyperbaric oxygen therapy (HBO) is a treatment in which patients breathe 100% oxygen while pressurized to a depth greater than sea level. The use of hyperbaric pressurization as a treatment for medical conditions dates back to the 1600’s, prior to the discovery of oxygen.9 Currently, HBO is used as a primary treatment for decompression sickness, air embolism, and carbon monoxide poisoning. It is also used as an adjunctive treatment for additional medical conditions including compromised grafts and flaps, chronic refractory osteomyelitis, and diabetic foot ulcerations (DFU). The Undersea and Hyperbaric Medical Society currently recommends the use of HBO as a treatment of the following conditions.10

1. Air or gas embolism
2. Decompression sickness
3. Acute carbon monoxide poisoning
4. Arterial insufficiencies, including enhancement of healing in selected problem wounds
5. Radiation-induced soft tissue and bone necrosis
6. Intracranial abscess
7. Clostridial myonecrosis
8. Necrotizing soft tissue infections
9. Compromised grafts and flaps
10. Crush injuries and compartment syndromes
11. Chronic refractory osteomyelitis
12. Thermal burns
13. Severe anemia where transfusion is impossible due to religious or medical concerns
14. Idiopathic sudden sensorineural hearing loss

HBO is administered while a patient is enclosed within a hyperbaric chamber. These chambers, composed of steel and acrylic components, are commonly located within outpatient wound centers in the United States and are utilized as an adjunctive wound healing modality. Monoplace hyperbaric chambers can accommodate one patient; multiplace hyperbaric chambers can accommodate multiple patients. In the United States, monoplace chambers are the most commonly encountered hyperbaric treatment vessels in hospital settings. During hyperbaric treatments, patients sit or lie supine in the hyperbaric chamber and breathe 100% oxygen for the duration of the treatment. Hyperbaric treatments are generally scheduled on a daily basis; most hyperbaric chambers in the United States operate during weekday business hours only, but some facilities may offer weekend or after-hours treatments for emergent conditions such as acute carbon monoxide poisoning. Each hyperbaric treatment is approximately two hours in duration; patients typically sleep or watch a movie during the treatment. The HBO treatment course is typically tailored to each individual patient; some patients may end their treatment course earlier than expected based on a more rapid course of healing or symptom resolution. Interestingly, despite the lengthy time commitment and need to present to the hospital for daily treatments, HBO has not been associated with decrements in patient quality of life.11 The use of traditional medical equipment and implanted devices in the hyperbaric environment poses unique challenges related to the inability of many modern medical devices (including intravenous pumps and ventilators) to withstand the typical pressurization encountered in the hyperbaric chamber. Most monoplace chambers are designed to treat the outpatient population only, as they are unable to accommodate patients who are undergoing treatment with mechanical ventilation or continuous intravenous infusions. Some implanted medical devices are unsuitable for use in the hyperbaric environment, due to fire safety concerns. Fortunately, many pacemaker manufacturers have tested their devices under pressure, and thus permanent pacemakers are often not regarded as a contraindication to hyperbaric compression. Topical oxygen therapy involves administration of oxygen via a bag, boot, or other device to a specific area of the body, most commonly the lower extremity. Advantages of topical oxygen therapy include a lower cost than traditional HBO, and ease of use: topical oxygen can be administered in an out-of-hospital setting such as a private residence or nursing facility.12 Unlike HBO, topical oxygen therapy is not associated with the potential for systemic oxygen toxicity. However, topical oxygen delivery systems generally do not achieve the high pressures found in hyperbaric chamber environments, and at this time there is not sufficient high-quality evidence to support the use of topical oxygen therapy as a medical treatment.12,13 Because of this, the procedure is often not reimbursed by insurance carriers.

In 1959, the Dutch surgeon Boerema published “Life without blood”, a manuscript detailing the use of HBO for the treatment of anemia.14 Boerema exsanguinated healthy piglets, and replaced the blood volume with a plasma-like solution. The piglets’ resulting hemoglobin concentration was 0.4 g/dL, a hemoglobin concentration that is incompatible with life. The piglets were then pressurized in a hyperbaric chamber to 3 absolute atmospheres (ATA) for 45 minutes. The animals survived this exposure, despite having essentially no hemoglobin present, and recovered uneventfully after they were re-infused with normal blood. Boerema noted that under hyperbaric conditions, the amount of oxygen dissolved in the plasma can greatly exceed the amount present while breathing air under normobaric conditions. This phenomenon is due to Henry’s Law, which states that the amount of gas dissolved in a solution is directly proportional to the partial pressure of the gas. When partial pressures of a gas increase, such as under hyperbaric pressurization, more of that gas dissolves in solution. Breathing room air (21% oxygen) under normobaric conditions results in a PaO2 of approximately 100 mmHg; breathing 100% oxygen under hyperbaric conditions results in a PaO2 of greater than 1600 mmHg.15 Under hyperbaric conditions, oxygen dissolved in the plasma can approximate or meet the body’s metabolic demands of oxygen extraction.16 This is the basis for the use of HBO for patients with severe anemia who are unable to receive transfusion. Since Boerema’s initial publication on this subject, there have been multiple reported cases of the use of hyperbaric oxygen therapy for the treatment of acute blood loss anemia in patients who are unable to receive transfusion of blood products.15-17 In these cases, patients received one to three HBO treatments daily; treatment frequency was based on the patient’s clinical presentation, and was titrated based on improvement or resolution of the signs and symptoms of oxygen debt. Currently, hyperbaric facilities across the United States continue to treat patients with acute blood loss anemia who are unable to receive blood transfusion due to religious or medical beliefs. A majority of insurance carriers, with the exception of the Centers for Medicare and Medicaid Services (CMS), consider hyperbaric oxygen therapy to be a medically necessary treatment for this patient population and will provide insurance reimbursement for this procedure.

The hormone erythropoietin (EPO) regulates red blood cell synthesis; the kidneys are the primary location of EPO release in adults.18 Intermittent hypoxia stimulates endogenous erythropoietin (EPO) synthesis, resulting in reticulocytosis and increased red blood cell production.18 Because of this mechanism, anemic bloodless medicine patients are often treated with exogenous EPO in an attempt to stimulate red blood cell production. Recently, intermittent normobaric hyperoxic exposures in healthy, non-anemic human subjects have been found to result in significant increases in endogenous EPO production and hemoglobin concentration.19 This phenomenon has been termed the “normobaric oxygen paradox”.19 It logically follows that patients who are exposed to intermittent hyperbaric oxygen may experience the same increases in reticulocytosis and hemoglobin concentration, but this has not been well studied. In one study, the administration of a single HBO treatment to healthy adult volunteers was found to decrease endogenous EPO production by 53%.20 However, the clinical implications of this study are unclear, as the majority of severely anemic bloodless medicine patients receive more than a single HBO treatment. The effect of serial HBO treatments on endogenous EPO production and subsequent reticulocytosis remains unclear at this time. At MedStar Georgetown University Hospital, preliminary data from bloodless medicine patients treated with HBO suggests that this treatment may actually stimulate erythropoiesis in patients with acute blood loss anemia, leading to faster resolution of anemia as well as potentially shorter hospital lengths of stay and decreased mortality.

Adverse effects of HBO are rare. Middle ear barotrauma is the most common complication of HBO; this is generally self-limited and can be prevented by carefully instructing patients on appropriate ear pressure equalization techniques. Central nervous system oxygen toxicity may result in seizures; however, seizures are rarely encountered in clinical hyperbaric practice. The risk of central nervous system oxygen toxicity may be reduced by the use of intermittent air breathing periods during each hyperbaric treatment. In diabetic patients, hyperbaric pressurization may result in hypoglycemia. Some patients may experience a temporary myopic shift during their hyperbaric treatment course, and patients with a history of anxiety or claustrophobia may exhibit confinement anxiety during hyperbaric treatments. Finally, as the hyperbaric environment is oxygen enriched by definition, fire safety is of paramount importance. Careful assessment and mitigation of any potential fire risk factors must be performed and maintained during each hyperbaric treatment. Fire-related fatalities have occurred in hyperbaric chambers due to the presence of static electricity, electrical shorts, and tobacco use within the hyperbaric environment.21 The National Fire Protection Association (NFPA) publishes standards for fire safety in health care facilities; hospital-based hyperbaric chambers must follow these standards. In accordance with NFPA regulations, patients may not wear garments of less than 50% cotton in monoplace hyperbaric chambers; in addition, patients may not bring cell phones, personal entertainment devices, personal warming devices, or any other items that may ignite or fuel a fire.22

When administered correctly, HBO is a safe procedure with minimal adverse effects. In patients with acute blood loss anemia who are unable to receive transfusion of blood products due to religious beliefs, HBO administration may result in improvement and/or more rapid resolution of the signs and symptoms of anemia. In the bloodless medicine patient population, adjunctive use of hyperbaric oxygenation in addition to standard bloodless medicine interventions can result in enhanced patient outcomes.

References

1. Van Meter KW. The effect of hyperbaric oxygen on severe anemia. Undersea Hyperb Med 2012;39(5):937-942.
2. Zeybek B, Childress AM, Kilic GS, et al. Management of the Jehovah’s Witness in obstetrics and gynecology; a comprehensive medical, ethical, and legal approach. Obstet Gynecol Surv 2016;71(8):488-500.
3. Weiskopf RB, Kramer JH, Viele M, et al. Acute severe isovolemic anemia impairs cognitive function and memory in humans. Anesthesiology 2000;92:1646-1652.
4. Klein HG, Spahn DR, Carson JL. Red blood cell transfusion in clinical practice. Lancet 2007;370:415-426.
5. Goodnough LT, Levy JH, Murphy MF. Concepts of blood transfusion in adults. Lancet 2013;381:1845-1854.
6. Chung KW, Basavaraju SV, Mu Y, et al. Declining blood collection and utilization in the United States. Transfusion 2016;56(9):2184-2192.
7. Petrini C. Ethical and legal aspects of refusal of blood transfusions by Jehovah’s Witnesses, with particular reference to Italy. Blood Transfus 2014;12 Suppl 1:s395-s401.
8. Resar LMS, Wick EC, Almasri TN, et al. Bloodless medicine: current strategies and emerging treatment paradigms. Transfusion 2016;56:2637-2647.
9. Edwards, ML. Hyperbaric oxygen therapy. Part 1: history of and principles. J Vet Emerg Crit Care 2010;20(3):284-288.
10. Weaver LK, ed. Hyperbaric oxygen therapy indications. Florida: Best Publishing Company;2014. P.iii.
11. Li G, Hopkins RB, Levine MAH, et al. Relationship between hyperbaric oxygen therapy and quality of life in participants with chronic diabetic foot ulcers: data from a randomized controlled trial. Acta Diabetol 2017;54:823-831.
12. Mutluoglu M, Cakkalkurt A, Uzun G, et al. Topical oxygen for chronic wounds: a pro/con debate. J Am Coll Clin Wound Spec 2015;5:61-65.
13. Anonymous. UHMS position statement: topical oxygen for chronic wounds. Undersea Hyperb Med 2018;45(3):379-380.
14. Boerema I, Meyne NG, Brummelkamp WK, et al. Life without blood (a study of the influence of high atmospheric pressure and hypothermia on dilution of the blood). J Cardiovasc Surg 1959;13:133-146.
15. Greensmith JE. Hyperbaric oxygen reverses organ dysfunction in severe anemia. Anesthesiology 2000;93(4):1149-1152.
16. McLoughlin PL, Cope TM, Harrison JC. Hyperbaric oxygen therapy in the management of severe acute anemia in a Jehovah’s Witness. Anaesthesia 1999;54:891-895.
17. Graffeo C, Dishong W. Severe blood loss anemia in a Jehovah’s Witness treated with adjunctive hyperbaric oxygen therapy. Am J Emerg Med 2013;31:756.e3-756.e4.
18. Rocco M, D’itri L, De Bels D, et al. The “normobaric oxygen paradox”: a new tool for the anesthetist? Minerva Anesthesiol 2014;80:366-372.
19. De Bels D, Theunissen S, Devriendt J, et al. The “normobaric oxygen paradox”: does it increase haemoglobin? Diving Hyperb Med 2012;42(2):67-71.
20. Balestra C, Germonpre P, Poortmans JR, et al. Serum erythropoietin levels in healthy humans after a short period of normobaric and hyperbaric oxygen breathing: the “normobaric oxygen paradox”. J Appl Physiol 2006;100:512-518.
21. Sheffield PJ, Desautels DA. Hyperbaric and hypobaric chamber fires: a 73-year analysis. Undersea Hyperb Med 1997;24(3):153-164.
22. National Fire Protection Agency. Chapter 14: hyperbaric facilities. In: NFPA 99 2015 Edition Health Care Facilities Code. Massachusetts: National Fire Protection Agency;2015. p. 105-117.

Download PDF version

HBO therapy has been used to treat children of all ages. In a study of children ages 2 months to 18 years, Dan Weisman et al. of the Israel Naval Medical Institute state: “The needs of the pediatric patient, especially the critically ill, require specific skills and equipment inside the hyperbaric chamber. Close collaboration between the pediatrician and the hyperbaric medicine physician is essential to ensure adequate care for infants and children.”

Hyperbaric Oxygen Therapy in the Pediatric Patient: The Experience of the Israel Naval Medical Institute, Dan Waisman, Avi Shupak, Giora Weisz, Yehuda Melamed. Pediatrics November 1998, VOLUME 102

The role of the hyperbaric nurse includes familiarizing patients with the hyperbaric environment, as many patients are unfamiliar with this treatment process and may have concerns about the procedure. The hyperbaric nurse monitors the patient during the hyperbaric treatments, and works closely with the hyperbaric medicine physician and other medical team members to ensure that the patient’s needs are met throughout the hyperbaric treatment process. The nurse should also monitor improvement in the patient’s physiological function after each hyperbaric session. The nurse can ascertain any subtle changes that may indicate an improvement in oxygen deficit. After each hyperbaric session the patient’s nurse should perform a specific assessment focusing on the patient’s tolerance of anemia. Vital signs, especially heart rate and respiratory rate are objective measures that show changes following hyperbaric therapy. The patient’s overall appearance, less pallor, and level of fatigue for ADLs (activities of daily living) are more subjective measures that can reveal a greater tolerance to anemia. This assessment information can be helpful to the medical team in making adjustments to the patient’s plan of care.

Dr. Johnson-Arbor reports a case in which hyperbaric oxygen therapy was used successfully when a Witness patient’s hemoglobin dropped precipitously during a CT-guided liver biopsy:

A 43 year-old female Jehovah’s Witness underwent an elective CT-guided liver biopsy. During the biopsy, she became hypotensive, presumably from hemorrhage. After resuscitation with intravenous saline and dopamine, she underwent emergent right hepatic artery embolization. Before the biopsy, her hemoglobin was 10.3 g/dL; after the biopsy, her hemoglobin reached a nadir of 4.6 g/dL, and she was tachycardic and complained of lightheadedness and weakness. Iron and erythropoietin infusions were ordered. Daily hyperbaric oxygen therapy treatment was initiated six days after the biopsy, with resultant decreases in the patient’s heart rate and improvements in her subjective complaints. The patient’s reticulocyte count was 1.7% prior to her biopsy and 4.8% two days after the biopsy. After HBO treatments were started, the reticulocyte count increased dramatically, reaching as high as 12.9%. The patient was eventually discharged from the hospital in stable condition, with a hemoglobin of 6.3g/dL.

This case and one reported in one of the articles cited by Dr. Johnson-Arbor show the lifesaving capability of hyperbaric oxygen in treating patients who experience sudden, critical blood loss:

McLoughlin PL, Cope TM, and Harrison JC in Hyperbaric oxygen therapy in the management of severe acute anemia in a Jehovah’s Witness. Anaesthesia 1999;54:891-895 report:

We describe the case of a 39-year-old African-American woman who developed sudden onset, near-term placental abruption with severe blood loss anemia whose religious beliefs precluded her from receiving any blood products. The patient had lost most of her blood volume, with a reported hemoglobin level of 1.9 g/dL, developed multisystem failure, and disseminated intravascular coagulation with bilateral deep venous thrombosis. Adjunctive hyperbaric oxygenation (HBO) therapy was considered, and the patient was referred for treatment. The patient required ventilatory support as well as vasopressors and hemodialysis. HBO therapy occurred in a monoplace chamber setting at 2.0 atmospheres absolute for 90 minutes per treatment up to twice daily depending on patient’s clinical status. The patient underwent a total of 30 HBO treatments and had sustained improvement in all hemodynamic parameters, red blood cell volume, renal and respiratory function. She was discharged to a rehabilitation facility on hospital day 29 and then to home, soon thereafter. The patient had no evidence of sustained physical or cognitive impairment at time of discharge, and there were no reported complications associated with HBO therapy. Adjunctive HBO therapy should be considered in the management of patients with exceptional severe blood loss anemia who refuse the use of blood products.

Manuel R. Estioko, MD is a Cardiac Surgeon from Los Angeles, California. He first developed an interest and involvement in Bloodless Surgery because of the very high incidence of Hepatitis C in open heart patients (18 % in New York City). At that time (late 1960’s & 1970):

• Almost all patients received blood transfusion, the early heart/lung machines required high volume prime with use of blood.
• Blood was obtained from donors with questionable health through commercial blood banking,  (the change to all volunteer donors came years later).
• There was no blood test for Hepatitis.

In 1996, Dr. Estioko coined and popularized the term “Transfusion Free Surgery” which is the other widely used designation for Bloodless Surgery.

All the patients in this report declined blood transfusion by reason of their religion; they were Jehovah’s Witnesses. Their decision was Bible-based and was not negotiable. The five major blood products that were not acceptable included: whole blood, plasma, red blood cells, white blood cells and platelets. Minor blood fractions, like coagulation factors, were considered a matter of conscience and most of the patients accepted them. Special informed consent forms were signed and witnessed. Face- to-face discussions between patient and surgeon were held two times or more. A close member or members of the family were encouraged to join in and all questions were answered to the patient’s satisfaction. These patients were well informed, most cooperative and very grateful.

The surgeon agreed to treat the patients with the above blood restriction. All the members of the surgical team including the anesthesiologist had agreed to this and all were committed to the goal of surgery without blood transfusion.  The surgeon provides strong leadership (captain of the ship) since he has the ultimate responsibility to the patient.

Cardiac surgery without blood transfusion was viewed as a total management approach that involves the three phases of care: preoperative, intraoperative, and postoperative.

• Appropriate surgical indication and timing of the operation.
• Maintain and optimize hemoglobin concentration
• Exclude bleeding problems.
• Associated medical conditions (comorbidities) are stabilized.

Anemia is the most important single predictor of blood transfusion in surgery. The additional blood loss during surgery worsens the anemia. None of our patients had preoperative anemia, all had normal levels of hemoglobin and hematocrit.

Primary Goals in Surgery

1. Limit blood loss with meticulous surgical techniques
2. Avoid coagulopathy by optimizing hemostasis and avoiding excessive hemodilution

Meticulous surgical technique with minimum blood loss

• Surgical team carefully plans the operation with all the details.
• Careful hemostasis during every step of the surgery.
• Use tools appropriately, i.e. electrocautery, suture, ligature, Argon Beam Coagulator (ABC), hemostatic glues and other preparations.
• Surgical team works efficiently, not hurriedly.

Even in cases of profound anemia, the body has a tremendous ability to compensate, resulting in a good prognosis for many profoundly anemia patients. This module will focus on fundamental physiological processes relevant to all types of anemia—the compensatory mechanisms that are triggered in the anemic patient.

A deeper understanding of the human body’s ability to compensate for profound anemia, in concert with modern non transfusion-based support modalities, has played a key role in a paradigm shift in the management of Jehovah’s Witness patients, as it has helped physicians to realize that a Witness patient’s conscientious refusal of blood transfusion does not preclude quality care.

The phrase “tolerance of anemia” has been used clinically in two interrelated ways, both of which are relevant to bloodless medicine and surgery:

1. the ability of the human body to compensate physiologically for anemia
2. a clinician’s decision to “tolerate” the patient’s anemia–not to automatically view subnormal hemoglobin or hematocrit numbers as requiring emergent intervention

According to the World Health Organization (WHO), anemia is defined as hemoglobin (Hb) levels <12.0 g/dL in women and <13.0 g/dL in men. However, normal Hb distribution varies not only with sex but also with ethnicity and physiological status, and the level at which patients become symptomatic varies according to the individual’s circumstances and capacity to respond to blood loss or reduced red cell production. Thus, for any patient, Hb values alone cannot provide the information needed to create an optimal care plan. Rather, it is essential that the physician take into consideration all the individual patient’s clinical signs and symptoms, and “treat the patient, not a number.”

This is important because many healthcare providers have a deeply held conscientious concern that a moderately or severely anemic patient requires urgent or emergent intervention. This can become particularly problematic when treating Jehovah’s Witnesses and other patients for whom blood transfusion is not an option. A well-intentioned physician or nurse unfamiliar with the compensatory mechanisms of anemia and the strategies of bloodless medicine may fear that a severely anemic patient is going to die imminently unless a blood transfusion is administered. These providers may spend considerable time and energy trying to convince or even coerce a patient to agree to a transfusion against the patient’s conscientious position and wishes. This reaction to an anemic patient can create stress for the provider that can complicate or impede the course of treatment. It may also translate into stress and/or harm to the patient—at very least by delaying appropriate care.

In a video interview found in our “Clinical Pearls” section, Dr. Hiep Dao describes a “paradigm shift” in patient care. High-quality research over the past two decades has demonstrated improved outcomes when less blood is transfused. A select group of providers have gained the skills and confidence needed to successfully treat patients for whom blood transfusion is not an option. Dr. Dao highlights the key role of education in achieving this paradigm shift. Education about the role of compensatory mechanisms in anemia is a key element of that education. Understanding the body’s ability to tolerate anemia helps the healthcare team to assess the patient’s anemia correctly and focus on providing optimal clinical care.

The Survivability of Profound Anemia: Understanding Compensatory Mechanisms

INTRODUCTION

We’ve learned a great deal about severe anemia from animal models. For example, in a porcine model of severe euvolemic anemia, evidence of lactic acidosis—which indicates insufficient tissue oxygen utilization—did not occur until a hemoglobin of 2.7 grams per deciliter. At a hemoglobin of 4, there was no statistical evidence of anemic hypoxic injury in the brain or heart, although other organs were less tolerant.

In humans, we have information dating back several decades indicating that many patients can survive illnesses associated with severe anemia. In fact, in postoperative patients, hemoglobin values as low as 2-3 gm/dl are associated with significant survival rates.

There are multiple databases that support the significant survivability of severe anemia. In one retrospective analysis of propensity-matched patients managed in a protocolized manner with hemoglobin less than 8, survival was similar in bloodless and transfused patients.

So the human body tolerates anemia even when hemoglobin is profoundly reduced. This is due to multiple compensatory mechanisms that help maintain adequate tissue oxygenation when the blood’s oxygen-carrying capacity is diminished.

These mechanisms include:

• Enhanced ability of hemoglobin to unload oxygen;
• Increased extraction of oxygen from the blood as it passes through capillaries;
• Increased cardiac output;
• And redistribution of that cardiac output.

Oxygen delivery to the periphery is determined largely by cardiac output or by means of convection. By the time oxygen reaches the periphery, the partial pressure of oxygen is quite low, and diffusion to the mitochondria where oxygen is utilized occurs down a relatively narrow gradient. The ability of hemoglobin to unload oxygen becomes all the more important when the system is stressed with severe anemia.

The oxygen hemoglobin saturation curve plots the proportion of hemoglobin in its saturated form on the vertical axis against the partial pressure of oxygen in the blood on the horizontal axis. A variety of factors can shift the curve. When shifted to the right, for example, by low pH, high temperature, or high carbon dioxide, oxygen becomes easier to unload and compensates for reduced convective delivery by anemia.

Normally, 25% of the arterial oxygen content is extracted by the peripheral tissues from each milliliter of blood. A reduction in delivery from a fall in cardiac output or anemia is associated with increasing extraction, allowing the body to maintain a normal oxygen consumption.

In the normal resting state, the heart pumps about five liters of blood every minute. When there is a greater demand for oxygen, as during exercise, the heart can increase its output many fold, to as much as 30 liters per minute.

During severe anemia, a rise in both stroke volume and heart rate contribute to an increase in cardiac output. Vasodilation and decreased blood viscosity are important components of this response.

In addition to increasing cardiac output, the body prioritizes the brain and heart. Control of peripheral vascular tone by the nervous system and other local mechanisms allows blood to be redistributed from less vital to more vital organs.

As a response to anemia, small blood vessels in the skin contract, causing a greater resistance to the flow of blood than is present in more vital organs. The result is a partial diversion of blood from the skin to other organs. Blood is also diverted from the kidneys as part of the adaptation to anemia.

The diversion of blood flow from the skin causes one of the cardinal clinical features of anemia: pallor. Pallor is the pale color observed in the skin of a light-skinned anemic individual, and in the mucous membranes and nailbeds of all anemic individuals, regardless of skin color.

It should be noted that anemic patients are pale not because their blood is thin but because the diversion of blood means there is less blood in the skin.

When these compensatory mechanisms are well understood, the care team will be able to operate on the basis of a new paradigm: finding appropriate and effective non-blood solutions instead of reflexively responding to anemia with blood transfusion or viewing transfusion as the sole treatment for anemia. The rationale for this approach is borne out by a large and increasing number of case reports and studies.

In Survival in Individuals with Profound Anemia Treated without the Use of Blood Transfusions, a study of patients undergoing a wide spectrum of medical, surgical and obstetrical cases, Patricia Ford et al. describe the non-blood techniques used in her hospital, demonstrating the survivability of profound anemia without blood transfusion: “Our nonblood approach included simultaneous interventions to stimulate erythropoiesis, control bleeding, enhance hemostasis, minimize iatrogenic blood loss and maintain hemodynamic stability. All patients received erythropoietin and iron with antifibrinolytic agents added for any active bleeding. To keep laboratory sampling at a minimum, physicians were required to rely on their basic clinical assessment skills to manage patients. The need for critical care monitoring, volume resuscitation and oxygen support was determined based on changes in blood pressure, heart rate, urine output, and cognitive function. Patients experienced slower recovery times with more frequent cardiac monitoring and increased length of hospital stays. This series demonstrates that the majority of individuals can survive with Hb levels as low as 2.5 g/dL utilizing simple nonblood strategies. The low mortality rate supports the elimination of any predetermined transfusion trigger.” Dr. Ford’s table summarizes patient outcomes at varying hemoglobin levels:

Table 1

Survival Rates in Patients with Profound Anemia

It is noteworthy that patients treated for anemia in a bloodless program who are stable and whose hemoglobin is rising are often discharged from the hospital with hemoglobin levels below 7, a level at which many providers would administer a blood transfusion.

Downloadable PDF version

The nurse’s role

Downloadable resources

We present a 36-year-old Jehovah’s Witness patient with complete placenta previa, placenta accreta, and a history of 2 prior C-sections who was transferred to MedStar Georgetown University hospital for management.  The patient was successfully treated with various disciplines working together as a team. Our multi-disciplinary approach involved the departments of obstetrics and gynecology, hematology, bloodless medicine, anesthesiology, urology, interventional radiology, and neonatology.

The Jehovah’s Witness surgical patient presents the surgeon and anesthesiologist with special medical and ethical considerations that arise from refusal of blood transfusion. There is great heterogeneity in blood product acceptance among antenatal patients of the Jehovah’s Witness faith. Jehovah’s Witnesses represent 0.8% of the US population.  Although some blood products are generally forbidden, such as red blood cells, granulocytes, plasma and platelets, the choice to accept or decline others, including the use of hemodilution and cell salvage, is left to the individual’s conscience.  The peripartum setting in a Jehovah’s Witness patient strikes fear in many surgeons’ hearts.  Candid preoperative discussion with the patient about the risks and options for bloodless care is essential in managing these patients.

Obstetrical hemorrhage is the leading cause of death during childbirth worldwide. Allogeneic transfusion has been a major factor for reducing the impact of hemorrhage in the peripartum period. The refusal of allogeneic transfusion presents a particular challenge for the Jehovah’s Witness patient, given the risk of hemorrhage andresulting potential for morbidity and mortality in both mother and fetus.  Combined with a placental abnormality such as placenta previa or placenta accrete, this risk escalates substantially.

A 38-year-old G6 P2033 with a history of two prior C-sections presented to our hospital transfer of care at 32+1 weeks due to complete placenta previa with possible accreta. The patient was a Jehovah’s Witness and refused blood products due to religious beliefs; she was transferred to take advantage of our bloodless medicine program.

Candid preoperative discussion with the patient about the risks and options for bloodless care is essential in managing these patients.

Upon evaluation by maternal-fetal medicine, the fetus was found to be growth-restricted at 3rd percentile during her 32+1 weeks ultrasound.

Delivery was recommended at 34 weeks with Betamethasone for fetal lung maturity prior to delivery.  Twice weekly antenatal testing was initiated. A bloodless medicine surgery program consultation was performed and the patient declined red blood cells, fresh plasma, and platelets.  The patient was willing to accept albumin, clotting factors, immunoglobulins, platelet gel autologous, sealants, and interferon. At 33+1 week she received an IV iron infusion per consultation with our bloodless team and outside consultation with Dr. Jonathan Waters, Chief of Anesthesiology at UPMC Magee-Womens Hospital, to increase her hematocrit and optimize cell salvage. Iron infusion approximately 10 days prior to the procedure had increased the patient’s hemoglobin and hematocrit from 12.9 mg.dL^-1/37.7% up to 13.2 mg.dL^-1/38.7%.

She was admitted for inpatient observation at 33+4 weeks.  An MRI was done, which showed iron deposits in the placenta due to patient’s iron infusion. This posed some challenges and difficulty in interpretation by the radiologist. An anterior placenta previa was confirmed, with edge of the placenta about 4 cm above the umbilicus.  The surgeon reviewed the MRI with the radiologist in order to provide the safest approach for uterine incision, to minimize cutting and separation of the placenta, and to decrease potential blood loss.  The fetus was found to be in a breech presentation. There was no evidence of placental invasion into adjacent pelvic structures but heterogeneity in the supra-vesicular region was concerning.

On the day of surgery the anesthesiologist went to the interventional radiology suite to place an epidural, and a hypogastric artery balloon was placed bilaterally. The patient was immediately transferred to the operating room for immediate cesarean section and hysterectomy.

The anesthesiologist proceeded to place arterial line and multiple large-bore catheters and initiated acute normovolemic hemodilution with a lower hemoglobin goal of about 10 mg.dL^-1. By intentionally diluting the intravascular red blood cell concentration, total cell mass loss per milliliter of surgical blood is reduced proportionately.

The patient was placed in a dorsal lithotomy position with the interventional radiologist in the operating room to position patient’s legs, to allow easy access to hypogastric artery balloon catheters in the event of severe hemorrhage.

A urologist performed cystoscopy and bilateral ureteral stent placement.  The cystoscopy was found to be unremarkable.

The neonatal ICU team was present intraoperatively to receive the newborn, perform resuscitation if needed, and transfer to the neonatal ICU. Gestational age at delivery was 34 weeks 5 days,

A midline vertical incision was done from 2 cm above the pubic symphysis to just above the umbilicus.  A fundal incision was made to avoid the placenta in the anterior location, and the fetus was delivered through this incision. Of note: for suction, a double setup system was used: one for the amniotic fluid, and the second for autologous blood salvage recovery after closure of the uterus.  Suction pressure was minimized unless severe hemorrhage ensued; this ensured that damage to recovered red blood cells was minimized.  A PDS loop suture in a running lock fashion was used to close the uterus with placenta still in situ.

We also rinsed all lap sponges in normal saline and suctioned via Cell Saver.  We set up a double suction so that most of the amniotic fluid was diverted into the wall suction system.  A Pall RS1 leukocyte applied patient filter was used after processing the salvaged blood.

We used the LigaSure device to incise the round ligament and develop the bladder flap bilaterally.  The ureteral stent was palpated throughout the procedure and noted to be out of the surgical field.  Bilateral utero-ovarian ligaments were cauterized and cut with the LigaSure device.  With the bladder dissected off the lower uterine segment below the level of the cervix, the uterine vessels were ligated bilaterally using Heaney clamps. On the left side the endometrium was significantly thin to the point where the placenta was practically visible.

It is important to note that upon placing Heaney clamps, the placenta must be avoided as much as possible, especially in placenta percreta, as this can cause significant bleeding and hemorrhage.  Our practice is to place the Heaney clamps below the edge of the placenta, at the internal cervical loss level if possible, to avoid significant bleeding.  This may be technically difficult.  A supracervical hysterectomy was completed and the urologist removed the ureteral stents.

At the end of the case, estimated blood loss was 1200 mL; the patient was stable and did not require re-infusion of the salvaged red blood cells (since salvaged cells have been processed and therefore there is a measure of risk in the re-administration of salvaged blood, and the patient’s condition did not require it, the decision was made not to re-infuse).  The interventional radiologist removed the balloons at the end of the procedure. Postop hemoglobin day 1 was 10.4 mg.dL^-1 and hematocrit was 31.8.

Postop was complicated by left leg weakness, which was evaluated by neurology.  This was believed to be the result of specific placement of the legs in the stirrups to allow access to the IR balloon without taking into consideration the wedge placed underneath the patient’s body at the beginning of the procedure, which distorted the angle between her body and her left leg.  The left leg weakness resolved spontaneously within the next few days. She was discharged home on postoperative day 4.

The purpose of this case report is to provide a guideline for multidisciplinary management of placenta previa in an obstetrical patient who declined blood transfusion due to religious beliefs, or for any other reason.

Developing a multidisciplinary, team approach to a very difficult and high-risk obstetrical case can maximize the chance of achieving an optimal outcome for a Jehovah’s Witness patient at risk for severe hemorrhage, as in placenta previa and placenta accreta, which put the patient at high risk for excessive intraoperative blood loss. Cell salvage technology has been applied in a variety of clinical situations but has not been used extensively in obstetric hemorrhage.  The justification for not applying cell salvage is a theoretical fear of reinfusing blood that contains amniotic fluid components, which could lead to an amniotic fluid embolism. Recent evidence suggests that cell salvage can be an important blood conservation strategy in the obstetric patient population.

Developing a multidisciplinary, team approach to a very difficult and high-risk obstetrical case can maximize the chance of achieving an optimal outcome for a Jehovah’s Witness patient at risk for severe hemorrhage.

It is important to mention the challenges that physicians face during this process.  Although behind the scenes, physicians are challenged by their concern for the patient’s safety as they accept and respect the patient’s decisions and work with the patient despite their apprehensions about the risk.  We are trained to manage medical problems according to standard protocols. It is vital to allow ourselves to realize “ Cura Personalis”: caring for the whole person requires that we recognize that there are beliefs behind life decisions that cannot be taken out of the picture.  Although candid discussion of the risks should be included in order for the patient to make an informed decision, ultimately the process of healing and success are dependent upon the patient’s trust in the physician’s capabilities and empathy, and the physician’s acknowledgment of and respect for the patient’s faith.  The goal is not to “scare” the patient and her family, but make them aware of risks while infusing trust and confidence in them. This patient communicated her fears with me every step of the way. Her previous physician had truthfully and correctly discussed with her the risks associated with refusal of blood transfusion, but did not take the time to instill a sense of trust in the patient. Trust in the physician’s capability of handling the medical obstacles without resorting to blood allows the patient to proceed with the reassurance that she will be optimally taken care of and that her choices will be respected. This level of empathy and trust can help the patient accept your recommendations and comply with your care.

Trust in the physician’s capability of handling the medical obstacles without resorting to blood transfusion allows the patient to proceed with the reassurance that she will be optimally taken care of and that her choices will be respected.

We believe that these general guidelines can be used in many patients for optimization starting in the antenatal period, regardless of their acceptance or non-acceptance of blood products:

1. Optimization of the patient’s blood levels in the antepartum. Recognizing the need for iron replacement therapy in oral form and if not tolerated, by intravenous infusions. Recognizing that newer Iron infusions have less allergic reactions.
2. Candid and empathic discussions with patient by our bloodless medicine team, the maternal-fetal medicine team, and a generalist OB/GYN were key factors.
3. Consultation with the bloodless medicine team to clarify patient’s blood product acceptance, plan for iron infusions, and coordinate the availability and use of the Cell Saver.
4. Anesthesia involvement with placement of appropriate lines for resuscitation, normovolemic hemodilution and appropriate fluid management, measures such as using tranexamic acid and uterotonic medications to decrease blood loss.
5. Interventional radiology placement of hypogastric balloon catheters.
6. Ureteral stents and evaluation of bladder by urology to assess for placental invasion and decrease risk of surgical damage.
7. Meticulous and appropriate surgical technique with preoperative planning of incisions, and involving an experienced surgical team. The team should include a GYN oncologist or general surgeon in anticipation of invasion of vital organs by the placenta, which is not usually managed by the generalist OBGYN.
8. Optimum positioning during potentially long procedures complicated by term pregnancy.
9. Cell salvage using a double setup and leukocyte depletion filtering in anticipation of the need for oral locus blood transfusion.  Good communication with an experienced cell salvage team and the use of normal saline to wash lap sponges and recycle via Cell Saver
10. Accurate estimation of blood loss.

Caring for these patients has given me the advantage of a new way of thinking that has enabled me to treat many of my patients without blood. This practice, developed for Jehovah’s Witnesses, has made its way into the management of my other obstetrical and also surgical gynecology patients. This new way of thinking and practice benefits not only my Jehovah’s Witness patients, but also all my patients, regardless of their faith.

A 22-year-old male Jehovah’s Witness was referred to a MedStar hospital with a bloodless medicine and surgery program from a hospital where transfusion was the only treatment option offered to him. His hemoglobin upon admission was 3.7. He was evaluated by the bloodless medicine and surgery team and was found to be profoundly iron deficient (ferritin level 1mg/ml, transferrin saturation 3%). Iron repletion and other supportive therapy corrected his anemia and he was discharged from the hospital with a hemoglobin level of 7.6; one week after discharge his hemoglobin was 10.3.

One of the “pillars” – the key principles – of bloodless medicine and surgery is managing anemia appropriately without blood transfusion. Much has been learned about how well the human body adapts to anemia, so that even profound anemia is shown to be survivable.

The case of “Brian Chen” well illustrates this principle. Other key principles of bloodless medicine and surgery will be highlighted throughout the case report.

A 22-year-old male Jehovah’s Witness with two prior episodes of coffee-ground emesis and extreme pallor was evaluated at a MedStar hospital where no bloodless protocol or program was available. Before the care team was aware that the patient was a Witness, they recommended blood transfusion. When they learned that the patient was a Witness, they promptly transferred him to the care of the Bloodless Medicine and Surgery Program at Georgetown University Hospital.

A first priority in bloodless medicine and surgery is to identify and stop any active bleeding. This strategy is highlighted in the document “Clinical Strategies for Managing Acute Gastrointestinal Hemorrhage and Anemia Without Blood Transfusion”. This strategy sheet advises:

Clinical Action Alerts:

• Patients who present with active upper or lower gastrointestinal (GI) bleeding represent a high-risk medical emergency that requires immediate aggressive intervention.
  
• The management priorities are to support the circulation and simultaneously identify and arrest the source of bleeding.
  
• Determination of the severity of bleeding should be based on the estimated magnitude of the initial hemorrhage and the rate of current bleeding. This can be ascertained from the history and physical examination, hemodynamic status, presenting symptoms, and endoscopic findings.
  
• In the bleeding patient, initial assessment can take place during resuscitation.

Mr. Chen’s evaluation upon admission to GUH revealed:

One month prior to admission, Mr. Chen experienced diarrhea and vomiting and thought the illness was likely due to a stomach virus. These symptoms appeared to resolve, but two weeks later, he experienced severe back pain. He took 200 mg of Tramadol, a mild narcotic, over 10 hours to help ease the pain. He then had an episode of coffee-ground emesis on the following day. Mr. Chen regularly took duloxetine for his chronic back pain and, in addition to this, had been taking about 600mg of ibuprofen, four times a day, for about a year.

• 22-year-old male with a history of scoliosis currently on Cymbalta.
• History of a prior lower gastrointestinal bleed approximately eight years ago.
• Presented to ED at an outside facility and with two prior episodes of coffee-grounds emesis. First episode was on Sunday prior to admission. After the episode on Sunday he reported no recurrence on the following day. However, two days later on Tuesday, which was the day of presentation to the outside facility, he experienced another episode of coffee-grounds emesis.
• Approximately two-to-three weeks prior to admission he had a gastrointestinal illness including diarrhea and some nausea. He denied any history of coffee-ground emesis at that time. He also denied any history of change in the color or consistency of his stools. He denied any black tarry stools.

• Blood pressure 99/50
• Pulse 127
• Extreme pallor and fatigue.
• Very thin male with pale conjunctivae.
• Oropharynx was clear.
• Pupils were equally round and reactive to light.
• Tachycardic, normal S1, S2. Presence of a flow murmur throughout.
• Lungs were clear to auscultation bilaterally. No wheezes or rhonchi.
• Abdomen was soft, was non-distended, non-tender to palpation with normoactive bowel sounds.
• Pulses were +2 throughout and no evidence of calf tenderness or lower extremity edema.
• Neurologic examination: He was appropriately conversant, moving all four extremities. Strength was 5/5 throughout.

By the time the patient was admitted to the ICU, his hemoglobin had dropped to 3.1. Despite this very low level of hemoglobin, his condition was stable; he showed no signs of confusion as he would have in the presence of lack of oxygen to the heart and brain. He showed signs of compensatory mechanisms due to his very low  hemoglobin. His pulse was elevated to 170-180. He showed no signs of active bleeding such as bloody stool. In view of his history of coffee-ground emesis, the care team suspected an upper GI problem. Taking these factors into consideration, the care team focused on stabilizing him, monitoring his vital signs every hour, and requested endoscopy and hematology consults (the latter because of his low platelet count).

The endoscopist did not agree to an exploratory procedure due to the patient’s very low hemoglobin. Although the risks of endoscopy are very low, since the patient had no buffer in case of an adverse event, endoscopy was postponed.

The hematology report came back negative for bone marrow disease. Lab tests revealed that Mr. Chen’s ferritin level was 1/mg/ml and transferrin saturation was 3%. These indicators of profound iron deficiency, along with the patient’s long- and short-term use of medications known to potentially cause bleeding as a side effect, were crucial for developing the treatment plan. As he did not show signs of active bleeding, the care team decided to wean the patient off his pain medications and administered folate, B12, IV iron, EPO and a PPI. He was given a single shot of 1000 micrograms of vitamin B12 and one 250 mg dose of IV iron daily for six consecutive days. He responded well to this protocol and his hemoglobin began to rise, indicating that his reticulocyte production was normal.

Within a few days it was clear that Mr. Chen’s urgent issues were being addressed effectively. His pallor, energy, and mood improved, and his hemoglobin continued to rise. It may require 24-48 hours for a patient to respond to iron supplementation, and the hemoglobin level may plateau and then suddenly jump. Mr. Chen’s hemoglobin at discharge was 7.6; one week after discharge it was 10.3, confirming the appropriateness and effectiveness of the treatment plan. Follow-up endoscopy after his discharge revealed eosinophil enteritis, a chronic auto-immune system disease that causes GI illness.

At most healthcare facilities, this patient would have been given a blood transfusion immediately. It has happened more than once that a patient in his condition has been told that without a transfusion they would die. In addition to violating the patient’s conscientious stand, blood transfusion would have raised the patient’s hematocrit only temporarily, and would have exposed the patient to the risks of transfusion without addressing the underlying issues of extreme iron-deficiency anemia and iatrogenic bleeding. Tolerating this otherwise stable patient’s low hemoglobin until the underlying cause of his anemia could be diagnosed and addressed led to optimal care.

No measures were taken by the bloodless care team that the first hospital could not have provided, had they been trained in bloodless medicine and surgery.

Bloodless Medicine and Surgery (BMS) is the provision of quality health care to patients without the use of allogeneic blood with the aim of improving outcome and protecting patients’ rights.^1,2 It involves the use of Blood Conservation techniques in combinations that are specific to the individual patient, ideally following a protocol and a multidisciplinary approach, and is synonymous with Transfusion-free Medicine and Surgery.^3,4

The term Patient Blood Management has crept into popular use in some circles, and has been recently defined by the Society for the Advancement of Blood Management as “the application of evidence-based medical and surgical concepts aimed at relying on a patient’s own blood rather than on donor blood and achieving better patient outcomes”.⁵ The basic principles or ‘pillars’ of Patient Blood Management were ratified by the 63rd World Health Assembly, and are identical to those of BMS as discussed herein.⁶

BMS has traditionally been considered in clinical situations where patients refuse blood, and when ‘safe’ blood is unavailable or in short supply.¹ Many clinicians are surprised to learn that blood transfusion is based on tradition and associated with a poorer outcome (unrelated to infectious hazards) in a wide variety of patients.⁷ Today, BMS has emerged as the standard of care appropriate for all patients because it is evidence-based and associated with a better outcome.¹

For about 2000 years up until the 19th century bloodletting rather than blood transfusion was the standard practice in medicine.⁸ Virtually all surgeries prior to the 20th century were essentially ‘bloodless’, and some were remarkably successful. Theodore Kocher, for instance, did his first thyroidectomy in 1872, and by the end of his career he had done 5000 thyroidectomies with only 1% mortality. Kocher never transfused any patient and he won a Nobel Prize.⁹

Karl Landsteiner’s discovery of the ABO blood groups in 1900 started off the modern era of transfusion medicine. In 1915 Richard Lewisohn introduced anticoagulation with sodium citrate. Blood transfusion was used for World War I and II military casualties. Bernard Fantus set up the first hospital based blood bank in Chicago, USA about 1937.10 From then on blood transfusion became a universal practice in medicine, so that the popular dictum seemed to be “When in doubt transfuse!”.³

BMS started as an attempt by some dedicated surgeons in the 1960s to accommodate patients who declined blood transfusion, notably Jehovah’s Witnesses.11, 12 Their religious belief is based on a distinctive interpretation of specific passages from the Bible, such as:

“You are to abstain from … blood” – Acts Ch. 15 v. 29 (New English Bible)^{13, 14}

Denton Cooley, widely regarded as the founding father of modern bloodless surgery, performed the first bloodless open-heart surgery on one of Jehovah’s Witnesses in May 1962.^{2, 12} In 1977 Ott and Cooley published a pioneer report of 542 open-heart surgeries without allogeneic blood transfusion in patients ranging in age from one day to 89 years,¹⁵ demonstrating that the “impossible” was possible – and safer. Other surgeons joined, but their ingenious techniques did not gain wide acceptance then.²

The advent of HIV/AIDS in 1981 forced a reconsideration of blood transfusion practices and a desire for BMS on account of the epidemic proportions of HIV, and the fact that the surest (though not the commonest) route of transmission is through blood transfusion. Many other pathogens old and new that are transmitted by blood (Table 1),¹⁶ and many non-infectious hazards (Table 2)¹⁷ received renewed attention and prominence. The cost of making blood “safe” rose astronomically while the supply of “safe” blood shrank. This added further impetus to the search for transfusion alternatives and the promotion of blood conservation techniques.^{1, 2}

Recently however, the focus has shifted from the hazards of allogeneic blood to its efficacy – or lack of it. The Canadian Critical Care Trials Group study on Transfusion Requirements in Critical Care (TRICC) by Hérbert and co-workers in 1999 was a landmark prospective randomized study of 838 ICU patients comparing a liberal transfusion versus restricted transfusion policy. It revealed better results with the restricted transfusion group: lower ICU mortality, lower hospital mortality, lower 30-day mortality, and a trend towards decreased organ failure.18 Several other studies have confirmed adverse outcome in transfused patients not related to infectious hazards.^19-24 Allogeneic blood has been found to increase hemorrhage, impair perfusion of the microcirculation, impair oxygen release from hemoglobin, and worsen rather than improve tissue oxygenation.^25-29 Some of these effects are thought to be due to storage lesions. On the other hand, it has not been possible to demonstrate the benefits of RBC transfusion.^{7, 19, 29, 30}

Thus, while BMS started as an advocacy and then became widespread because of the infectious hazards and high cost/scarcity of allogeneic blood, Evidence-Based Medicine has recently emerged as the driving force behind its current practice, with improvement of outcome as the major aim.

Blood conservation techniques form the basis of the practice of BMS, and may be grouped under of four basic categories or “pillars”:³

1. Optimizing the Hematocrit
2. Minimizing blood loss
3. Optimizing tissue oxygenation
4. Lowering the ‘Transfusion Trigger’ (tolerance of anemia)

Table 1. Infectious agents transmissible by blood transfusion¹⁶

Any hospital can practice bloodless medicine, as this area of medicine does not always need to involve advanced techniques, expensive equipment, or esoteric methods of patient care. In many cases, optimization of bloodless medicine patient care can be managed with a careful review of current medical practices. Laboratory testing is a great example of this: we order labs on most hospitalized adult patients each day as a routine, but this practice has been associated with increased needs for transfusion in some patient populations.¹ Hospital-acquired anemia, which can occur as a consequence of daily routine blood draws, is associated with increases in-hospital mortality and resource utilization.² In the bloodless medicine subset of patients, daily phlebotomy may cause excessive and unnecessary blood loss which may be harmful. 

It is important to remember that the bloodless medicine patient can remain alive without receiving blood. Although it may seem impossible to many of us, patients do survive without receiving blood transfusions for acute blood loss anemia with hemoglobin concentrations as low as 3-4 mg/dL. We learn early in our training that acutely anemic patients should receive blood transfusions, but we do not learn how to manage patients who cannot receive such transfusions. 

When blood transfusion is unable to be performed on a patient due to medical or religious reasons, members of the medical team may react with frustration or anger. In some cases, the focus on the perceived need for transfusion may distract the medical team from ordering other consultations or procedures that could be performed to control active bleeding. There are many simple interventions that can be implemented as soon as the patient arrives at the hospital, to reduce the indications for blood transfusion and optimize care of the bloodless medicine patient.

Typical vacutainers can hold anywhere from 2-10 milliliters of blood. Phlebotomists often draw a “rainbow” of 7 vacutainers in the Emergency Department in anticipation of tests being ordered by a physician, and this can result in an acute blood loss of 20 or more milliliters from one phlebotomy draw. In one study of transfusion practices in ICU patients, phlebotomy draws resulted in blood loss exceeding 70 milliliters per day.³ For the bloodless medicine population, utilization of a careful phlebotomy technique with attention to the number of vacutainers used can result in reduced unnecessary blood loss. Instead of directing a phlebotomist to draw a “rainbow” of tubes, we can consider asking the phlebotomy staff to hold off on drawing blood until a physician has evaluated the patient (a “bloodless medicine” wristband, bedside sign, or other identification method can be created for the patient at triage in order to alert hospital staff of the patient’s status). Then, based on the physician’s evaluation, a focused phlebotomy attempt can be performed. In addition, the choice of vacutainer can affect the phlebotomy amount. Pediatric microtainers, which hold 200-600 microliters of blood, can be substituted for typical vacutainers in the bloodless medicine population, additionally reducing unnecessary blood loss. Point-of-care testing, which requires significantly reduced quantities of blood for analysis compared with traditional phlebotomy, is another option for laboratory testing in the Emergency Department. 

We suggest that Emergency Departments consider implementation of both focused phlebotomy techniques and use of pediatric microtainer tubes or point-of-care testing, in the bloodless medicine population.

Along with the volume of blood drawn, the frequency of blood draw attempts can also contribute to iatrogenic acute blood loss.  Computerized entry sets for laboratory orders often default to a daily frequency for blood draws, but daily labs are not often needed in every patient. For the bloodless medicine population, a simple change in the frequency of blood draws from every day to every other day can result in a reduction in blood loss that can be potentially life-saving. We must think about why we are ordering labs, and not just what we are ordering. For many bloodless medicine patients, especially those who are admitted due to complications of acute anemia, checking a daily complete blood count will not change the treatment plan since transfusion is not an option. Thus, it is completely reasonable to check labs every 2-3 days, or even less frequently, in this patient population.

Human erythrocytes take approximately one week to mature.⁴ For short-term monitoring in the bloodless medicine patient who is already being treated with erythropoietin and/or other hematinic agents, hemoglobin and hematocrit concentrations are of low utility due to the known length of time required for red blood cell maturation. Other laboratory parameters, such as the automated reticulocyte count, can be useful as adjunctive assays for quantifying a patient’s erythropoietic response. Additional reticulocyte assays, including the reticulated hemoglobin, absolute reticulocyte count, and immature reticulocyte percentage, may also be helpful when attempting to quantify the degree of erythropoiesis in a bloodless medicine patient. 

For example, even though a patient’s hemoglobin may remain stable over a period of days, serial increases in the above reticulocyte assays during this time indicates that erythropoiesis is actively occurring and that an elevation in hemoglobin concentration is likely to occur in upcoming days (assuming that any acute bleeding has ceased). This information is reassuring to both the physician and the patient, can be used for discharge planning purposes, and may even translate into reduced lengths of hospital stay for bloodless medicine patients. 

While the judicious use of laboratory monitoring is a critical concept in the management of the hospitalized bloodless medicine patient population, the importance of interpersonal interactions with bloodless medicine patients is infrequently discussed but also requires attention. Bloodless medicine patients, and specifically the Jehovah’s Witness population, are an educated and knowledgeable group of patients. Jehovah’s Witnesses are keenly aware of the risks of not accepting blood products, including the risk of death. As physicians, our beliefs regarding blood transfusion may differ from those of the Jehovah’s Witness population; however, each of us is entitled to our own beliefs, and one belief is not necessary superior to another. As physicians, we must accept the beliefs of patients, even when they differ from ours, and treat the patient according to their beliefs, not ours. It is the patient who is receiving the treatment; therefore it is the patient’s informed choices that have ethical and legal control. 

All too frequently, patients who are transferred to my institution for bloodless medicine services will tell me that another doctor told them they “would die” if they did not receive blood or that there is “nothing else that can be done” for the patient because they were not able to receive blood. Some patients have left the original hospital against medical advice after being pressured to receive a blood transfusion with no alternative methods of treatment offered; this unfortunately resulted in further delays in their medical care. 

As has already been discussed, there is always something that can be done; any hospital, regardless of size or academic reputation, has resources available to treat the bloodless medicine population. Interventions as simple as acknowledging a patient’s religious beliefs by placing a “bloodless medicine” wristband on the patient and a similar sign on the door to reduce unnecessary phlebotomy attempts, are not only beneficial in the overall treatment of bloodless medicine patients; these interventions can also subtly alert the patients that we are working with them, not against them, for their medical care. 

The concept of “working with the patient” is crucial in the treatment of bloodless medicine patients. If a physician attempts to convince a Jehovah’s Witness patient to accept blood either actively (by repeatedly telling the patient that they need a blood transfusion) or passively (by telling the patient “you may die” or “there is nothing else that can be done”), the patient’s appropriately negative response may be recorded in the medical record as an example of noncompliant behavior. The term “noncompliant” has a negative connotation in the medical field and may lead to conscious or implicit bias and disparities in the quality of patient care. 

For a patient, the description of noncompliance may, in turn, lead to impairments in the relationship between the patient and the other members of the medical team, further breakdowns in communication, and marginalization of the patient and his/her needs. 

Instead of assigning the description of noncompliance to patients who are unable to receive blood transfusion due to religious reasons, it is more beneficial to acknowledge the patient’s difference in beliefs and implement a treatment plan that takes the religious beliefs into consideration. The ultimate treatment plan may not be the easiest or the fastest (i.e., it may involve the use of erythropoietin, hematinic agents, and hyperbaric oxygen therapy instead of a blood transfusion), but it will share the same goals of care while respecting the patient’s religious autonomy. 

If a physician, for whatever reason, is not able to care for a patient without the use of blood transfusion, the patient should be referred or transferred immediately to a physician or hospital willing and able to provide appropriate care. Failure to act promptly may result in harm to the patient. 

We know that severely anemic patients can survive without receiving blood transfusions; simple recognition and acceptance of this fact allows us, as treating physicians, to consider other currently available options to minimize blood loss and augment erythropoiesis.  Basic interventions, such as limiting unnecessary blood draws and understanding which laboratory assays are most relevant for a particular patient population, can greatly enhance our ability to care for those for whom blood transfusion is not an option. 

These same techniques can also be applied to our daily medical practice for all patients, and can result in reductions in hospital-acquired anemia, avoidance of transfusion-related complications, and optimized outcomes for all of our patients.

The practice of bloodless medicine does not have to be a difficult or complex process. It does require a willingness on the part of the doctor to respect the patient’s choices, review current medical practices, and creatively find new plans for care. Clinicians who do these things earn their patients’ gratitude and deep respect.

A Bloodless Medicine and Surgery Program (BMSP) is a multidisciplinary team approach designed to meet the needs of Jehovah’s Witnesses and other patients seeking optimal medical care without the use of blood transfusion. Some patients admitted to your hospital will resolutely object to the use of blood or blood components as a medical treatment option, even in a life-threatening situation. This refusal may be based on religious, personal, or other conscientious reasons.

FEATURED MEDSTAR EXPERT

Dick Verstraete, Nurse Coordinator of the Bloodless Medicine and Surgery Program at MedStar Georgetown University Hospital, Washington, D.C., USA, explains the benefits of having a BMSP at your hospital:

There are eight and a half million Jehovah’s Witnesses in the world. There are also a large number of patients for whom blood transfusion is not an option for other reasons, such as blood availability, and a growing number who choose to avoid transfusions due to risk. Healthcare professionals need to provide optimal care for all such patients.

When I first cared for a bloodless patient as a cardiac nurse, I had no idea what to do if the patient’s hemoglobin dropped. Our fallback was blood transfusion, and we had no other plan of care for this patient. So I set out to develop a plan that would help the bedside nurse know how to respond when situations arose that threatened to compromise the care of a bloodless patient in the postoperative recovery period after major cardiac surgery.

It was my concern for the welfare of these patients that led our care team to develop bloodless protocols and strategies.

CD Sharman, writing in the American Journal of Hematology, reported on his experience at the Oregon Science and Health University Hospital in Portland, OR USA: “We have found that medical and administrative efforts in the form of bloodless medicine and surgery programs can be instrumental in helping to reduce risks of morbidity and mortality in [Jehovah’s Witness] patients.”

Since bloodless care requires awareness of the patient’s needs and appropriate training for all members of the healthcare team, a cultural shift within the hospital or other healthcare institution is needed to ensure consistent quality of care. A BMSP helps to facilitate the coordination of care across all disciplines and eases the cultural transformation in our current patient care model.

A significant side benefit to the healthcare institution is that when providers see for themselves the excellent results that can be achieved without incurring the costs and complications of blood transfusion, they readily transition to using bloodless strategies for all their patients, thereby improving quality and safety and reducing costs.

In the words of Stephen R.T. Evans, MD, Chief Medical Officer for the MedStar Healthcare System, “Building a toolbox to manage the Witness community benefits all our patients.”

The BMSP places the bloodless patient’s autonomy at the forefront of the plan of care, with the goal of honoring the patient’s rights and wishes. Optimal care of the bloodless patient demands a genuine commitment to the process of shared decision-making, which is a fundamental focus of MedStar’s Institute for Quality and Safety. Healthcare providers must have not only a thorough grasp of the tools and techniques of bloodless medicine and surgery, but also a complete understanding of the patient’s personal choices regarding the acceptability of various procedures and pharmaceutical products.

The staff of a BMSP can facilitate the shared decision-making process by providing clarity and comfort for both physician and patient in crafting a care plan that meets the patient’s needs.

Highlighted below are some key elements for establishing a bloodless medicine and surgery program.

1. Administrative support: The program must have an administrative champion with the authority needed to initiate and implement the program.

2. Business plan: Your business plan should describe the program benefits, limitations, and possible rewards (sample business plan included in downloadable documents).

3. Outreach to your local HLC: The local Hospital Liaison Committee (HLC) of Jehovah’s Witnesses is available to make presentations to individual physicians or entire departments. These presentations will help hospital staff better understand the conscientious position of Jehovah’s Witnesses. .

4. Determining level of interest within the hospital: The champion must identify physicians willing to support the program in order to form an effective, multidisciplinary bloodless care team.

5. Expanding your physician base: Engage the medical staff in informal settings to determine level of interest, and discuss any concerns.

All nurses involved in the patient’s care should have the skills needed to provide a safe healing environment and advocate for the patient, ensuring that the patient’s wishes and dignity are at the center of the care plan. Throughout the patient’s hospitalization the nurse on duty should act as gatekeeper, being constantly vigilant to make sure the patient does not inadvertently receive a transfusion or other intervention that goes against the patient’s wishes. The nurse should also protect the patient against all attempts, no matter how well intentioned, to convince the patient to accept an intervention other than those agreed upon in the care plan. 

Care of the post-surgical patient requires the nurse to be vigilant to recognize signs of covert bleeding and to notify the surgical team immediately. During patient rounds the nurse provides vital information on the patient’s status. The nurse should also ensure that measures are taken to avoid hospital-acquired anemia by recommending the use of small-volume sample tubes for all blood draws and eliminating routine labs.

In addition, with change of shift, it is important to communicate to the oncoming nurse the patient’s care plan, and to be sure that all involved with the patient’s care are aware that the patient in enrolled in the bloodless program.

Here are some lessons we learned in setting up a BMSP at MedStar Georgetown University Hospital:

Once the decision has been made to develop and implement a BMSP, logistical issues need to be addressed, These include staffing priorities and work space accommodations.

STAFFING

Medical Director: The key element for this position is choosing a physician from the current medical staff who is enthusiastic about the program, committed to its success, and willing to advocate for the bloodless patient.

Program Coordinator: In order to build a successful program, a full-time, dedicated coordinator is required. This position has been staffed in other BMSPs with individuals from varying backgrounds. One of the most important considerations is hiring a Jehovah’s Witness to fill the position. The JW community will be more supportive from the outset and this will provide a level of trust for the new program. Some hospitals have succeeded in finding a Witness program coordinator already working at their institution in another department. You may also ask your local Hospital Liaison Committee if they know of someone who would fit the role.

Nurse Coordinator: The second consideration is hiring an experienced registered nurse or nurse practitioner. Being a former critical care nurse helped in my consulting with physicians on the care of the bloodless patient. As a non-Witness nurse in this position, it was very difficult for me to gain the trust of the Witness community. Over time I have overcome that issue by being caring and a strong patient advocate.

Finally, in my opinion, the ideal candidate for the Coordinator position would be a nurse practitioner who is a JW. My major regret in caring for bloodless patients is not being able to write orders, as this ability would allow me to be directly involved with more aspects of their care.

PROGRAM DESIGN LOGISTICS

Once the program has received the green light, a medical director has been chosen, and the program coordinator has been hired, it is now time to lay the foundation for sustaining a successful program.

In our case a steering committee was formed to provide feedback and advise. Our steering committee consisted mainly of physicians from various hospital departments. The one drawback of our committee was that it lacked strong nursing leadership. Should you decide to have a steering committee, we advise you to include representatives from the following areas: transfusion services, nursing, anesthesia, surgical services, medical services, obstetrics, oncology, and pharmacy. Our committee was chaired by the hospital vice president of medical affairs, who was a strong advocate of the BMSP.

Secure office space and begin operations.

All of the following essential documents are provided as downloads to assist you in building your own BMSP blueprint. If you have developed a unique blueprint for your BMSP, please share it with us so others may benefit.  

Procedures and  Job Aids: Policy and procedure

• P&P: Understand regarding refusal of blood transfusion for minors
• Medical Director’s Job Description
• BMSP Monthly Report
• Introduction to the BMSP Patient Instruction Sheet
• BMSP Instructions of Patient Consent
• Personal Choice Medical Treatments
• MITC BMS Blood Fractions
• Cell Salvage Process
• Job Aid Determining Transfusion Alternatives
• Job Aid Anemia Management in Nonbleeding Patients
• Job Aid Anemia Management in Bleeding Patients
• Job Aid Preop Anemia Management
• Cesarean Birth Postpartum Hemorrhage Protocol
• Five things to Know about the BMSP at MGUH
• Ped Tubes sign
• Anemia brochure
• Bloodless Kidney Transplant Flyer

Patient Education Materials

The following short videos and infographics are provided to help your patients in making decisions about procedures and products that may be offered at your hospital:

What is bloodless medicine and surgery?

HISD Strategy Protocols

Links to strategy protocols created by the Hospital Information Services Department at Jehovah’s Witnesses’ World Headquarters:

• Blood Transfusion Alternative Strategies
• Critically Ill Patients
• OBGYN Hemorrhage Anemia
• Religious and Ethical Position Medical Therapy
• Clinical Strategies Avoid Blood Transfusions
• Avoid Control Hemorrhage Anemia
• Hospital Liaison Committees Jehovah’s Witnesses

Download PDF version

Medical evidence has been accumulating over recent decades associating blood transfusion with increased risk; but that knowledge has not made a proportionate impact on medical training and clinical care. Blood transfusion is still viewed by many healthcare providers as the only viable, scientifically sound and responsible option in many clinical scenarios. This strongly held conviction on the part of the provider may at times result in an adversarial stance toward the patient who chooses to decline transfusion, which may in turn bring stress to the provider and harm to the patient.

It is hoped that a heightened awareness of the risks of blood transfusion along with a better understanding of the body’s tolerance of anemia, will help providers to see that bloodless care is a reasonable, responsible choice. Such awareness and understanding has proven to eliminate unnecessary friction in the doctor-patient relationship for healthcare providers who treat Jehovah’s Witnesses.

Early Complications:

    Hemolytic reactions (immediate and delayed)

    Non-hemolytic febrile reactions

    Allergic reactions to proteins, IgA

    Transfusion-related acute lung injury

    Reactions secondary to bacterial contamination

    Circulatory overload

    Air embolism

    Thrombophlebitis

    Hyperkalemia

    Citrate toxicity

    Hypothermia

    Clotting abnormalities (after massive transfusions)

Late complications:

    Transmission of infection

        Viral (hepatitis A, B, C, HIV, CMV)

        Bacterial (Salmonella)

        Parasites (malaria, toxoplasma)

    Graft-vs-host disease

    Iron overload (after chronic transfusions)

    Immune sensitization (Rhesus D antigen)