Continuing Education Activity

Red blood cells transport oxygen via hemoglobin. A reduction in hemoglobin levels causes anemia, often leading to signs and symptoms of inadequate tissue oxygenation, commonly referred to as an oxygen debt. Clinical manifestations include tachycardia, dyspnea, fatigue, chest pain, and altered mental status. Laboratory findings may show metabolic acidosis, hyperlactatemia, and elevated cardiac enzymes. Symptomatic patients typically receive packed red blood cell transfusions to restore oxygen-carrying capacity. However, transfusion may be contraindicated in individuals with religious objections or specific medical conditions. In such cases, hyperbaric oxygen therapy (HBOT) offers an alternative approach to enhance tissue oxygen delivery and alleviate symptoms associated with oxygen debt.

This activity provides healthcare providers with the knowledge and skills to administer HBOT and identify patients with blood loss anemia who are suitable candidates for this intervention. This activity also covers relevant physiology, as well as the indications, contraindications, and proper implementation of HBOT. In addition, this activity highlights the importance of interprofessional collaboration among healthcare providers for treating individuals with blood loss anemia, ultimately improving patient outcomes.

Objectives:

• Identify patients with blood loss anemia who may benefit from hyperbaric oxygen therapy, including those who refuse blood transfusions.
• Implement individualized hyperbaric oxygen therapy protocols based on the patient's clinical status and the severity of their anemia.
• Apply adjunctive therapies, such as nutritional support and blood conservation techniques, to optimize patient outcomes during hyperbaric oxygen therapy.
• Collaborate with interprofessional healthcare team members to ensure continuity of care for patients requiring repeated sessions.

Introduction

Hemoglobin, found in red blood cells, is the primary carrier of oxygen in the human body. A reduction in hemoglobin levels results in anemia, which can impair tissue oxygenation and lead to an oxygen debt. Clinical manifestations of this condition include tachycardia, dyspnea, fatigue, chest pain, and altered mental status. Laboratory findings may reveal metabolic acidosis, elevated lactate levels, and increased cardiac enzymes. Symptomatic patients are typically treated with packed red blood cell transfusions to restore oxygen-carrying capacity. However, transfusion may be contraindicated in certain individuals, such as those with massive autoimmune hemolysis or those who decline blood products for religious reasons.[1] In such cases, hyperbaric oxygen therapy (HBOT) can enhance oxygen delivery to tissues and help relieve the symptoms of oxygen debt.

Etiology

According to the doctrine of Jehovah’s Witnesses, certain Bible passages—such as those found in Genesis, Leviticus, and Acts—command followers to abstain from receiving blood. As a result, Jehovah’s Witnesses decline blood transfusions, a stance that has been recognized and upheld by the American legal system.[2] Other patients may be unable to receive blood products due to medical reasons, including hemolysis, the development of antibodies following transfusion reactions, or crossmatch incompatibility. Individuals who cannot accept transfusions for religious or medical reasons face a heightened risk of morbidity and mortality following acute blood loss, such as that caused by postpartum hemorrhage, trauma, or intraoperative bleeding.

Epidemiology

Up to 1000 Jehovah’s Witnesses die each year, partly because they refuse to accept blood transfusions. Patients who are older or have conditions such as obesity, dependence on hemodialysis, or underlying heart disease face an increased risk of mortality when affected by anemia.

Pathophysiology

HBOT is administered in a hyperbaric chamber, where the patient breathes 100% oxygen at pressures greater than 1.0 atmosphere absolute (ATA), typically ranging from 2 to 3 ATA. Pressures exceeding 3 ATA are associated with an increased risk of oxygen toxicity.

Oxygen delivery (DO₂) to tissues depends on arterial oxygen content (CaO₂) and cardiac index (CI). This relationship is represented by the following equation:

DO₂ = CaO₂ × CI

Arterial oxygen content (CaO₂) primarily depends on hemoglobin concentration. Each gram of hemoglobin can carry up to 1.38 mL of oxygen. A small fraction of oxygen is dissolved in plasma, which is influenced by the partial pressure of oxygen in blood (PaO₂). The equation for calculating arterial oxygen content is as follows:

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

Tissues extract approximately 5% to 6% of the oxygen content from circulating blood.[3] Symptoms of oxygen debt occur only when oxygen supply fails to meet tissue demand. In individuals with anemia, oxygen delivery via hemoglobin may become inadequate. When hemoglobin levels fall below 6 g/dL, oxygen delivery is insufficient to meet metabolic requirements. At levels below 4 g/dL, tissue oxygenation is severely compromised.

In 1959, Dutch surgeon Ite Boerema published “Life Without Blood,” a landmark study that described the use of HBOT in the treatment of anemia.[4] In his experiments, healthy piglets were exsanguinated and their blood volume replaced with a plasma-like solution, resulting in hemoglobin concentrations as low as 0.4 g/dL—levels typically incompatible with life. The piglets were then placed in a hyperbaric chamber at 3 ATA for 45 minutes. Remarkably, despite the near absence of hemoglobin, the animals survived the exposure and recovered fully after receiving a transfusion of normal blood.

Boerema observed that under hyperbaric conditions, the amount of oxygen dissolved in plasma could far exceed that found when breathing air at normal atmospheric pressure. This phenomenon is explained by Henry’s Law, which states that the amount of gas dissolved in a liquid is directly proportional to the partial pressure of the gas. As the partial pressure increases during hyperbaric pressurization, a greater amount of oxygen dissolves into the plasma.

Breathing room air (21% oxygen) at normal atmospheric pressure yields a PaO₂ of approximately 100 mm Hg. In contrast, breathing 100% oxygen under hyperbaric conditions can elevate PaO₂ to above 2000 mm Hg. At 3 ATA, the amount of oxygen dissolved in plasma can reach approximately 6% of total blood volume—closely matching the typical oxygen extraction by body tissues. Under these conditions, plasma-dissolved oxygen alone can meet or nearly meet the body’s metabolic oxygen requirements, even in the absence of adequate hemoglobin.[5][6]

History and Physical

Anemia can present with a broad spectrum of signs and symptoms. Affected individuals may experience lightheadedness, confusion, weakness, fatigue, irritability, headaches, decreased exercise tolerance, palpitations, or dyspnea. These symptoms typically do not appear until the hemoglobin level drops below 7 g/dL.

The most common sources of blood loss in the human body involve the gastrointestinal, genitourinary, and pulmonary systems. As such, it is important to obtain a thorough menstrual history in women and to inquire about symptoms such as hematemesis, hemoptysis, hematuria, hematochezia, and melena.

A comprehensive past medical history should include:

• Medications: Certain medications, including aspirin, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, bisphosphonates, carbamazepine, cephalosporins, nonsteroidal anti-inflammatory drugs (NSAIDs), phenytoin, sulfa drugs, and chemotherapy agents, can affect hematological status.
• Supplements: Iron, folate, and vitamin B12 may influence anemia status or mask deficiencies.
• Family history: Conditions such as sickle cell anemia, glucose-6-phosphate dehydrogenase deficiency, and hereditary spherocytosis should be assessed.

On examination, acute hemorrhage causing emergent anemia may present with hemodynamic abnormalities, such as hypotension, tachycardia, and tachypnea. Patients may also experience decreased urine output, increased thirst, and altered mental status. The clinical presentation can vary based on comorbidities, age, baseline medications, and the severity of illness. Younger adults often compensate with an elevated heart rate, whereas older adults, particularly those taking β-blockers, may exhibit a blunted compensatory response.

In chronic anemia, physical examination is often unremarkable but may reveal signs suggestive of specific underlying causes. Pallor, scleral icterus, and jaundice are indicative of hemolytic anemia.

Physicians should assess for cardiac murmurs, pulmonary crackles, hepatomegaly or splenomegaly, thyromegaly, joint deformities, and lymphadenopathy. An anorectal examination should evaluate for tenderness, perianal rashes, and the presence of melena or visible blood. Chronic anemia accompanied by signs of bleeding may suggest an underlying coagulation disorder. Patients may tolerate hemoglobin levels as low as 5 to 6 g/dL if the anemia develops gradually.

Evaluation

Patient evaluation should focus on signs and symptoms of impaired oxygen delivery to tissues. Vital signs may reveal tachycardia and hypotension. Changes in mental status can occur, with the risk of cerebral infarcts due to reduced brain oxygenation. Electrocardiography may demonstrate ischemic changes, and decreased urine output often reflects hypoperfusion. Laboratory findings can include metabolic acidosis, elevated cardiac enzymes, and a base deficit.

Treatment / Management

The physiological effects of HBOT in anemic patients are short-lived, with elevated tissue oxygen partial pressures lasting only minutes to hours following each session. The frequency of HBOT should be individualized based on the patient’s clinical status.[7] Patients with more severe symptoms may require therapy 2 to 3 times daily. Standard treatment protocols typically involve exposures at 2 to 3 ATA for 3 to 4 hours, administered 3 to 4 times daily. Notably, it is essential to maintain adequate volume status and provide nutritional support, including hematinics such as folic acid, B vitamins, and iron.[8]

Treatments may be delivered in either a monoplace (which accommodates a single patient) or a multiplace (which can treat multiple patients) hyperbaric chamber. Treatment depths vary according to each hyperbaric unit’s protocols; however, deeper treatments result in higher oxygen partial pressures and are more likely to relieve symptoms of oxygen debt. Additional modalities that reduce oxygen consumption, such as sedation, neuromuscular paralysis, and cooling, may be used as adjunctive therapies. Blood loss should be minimized whenever possible, with pediatric tubes used during phlebotomy to reduce unnecessary blood volume loss.[9] Consultation with a bloodless medicine specialist may also be considered for guidance on iron supplementation and erythropoietin therapy.[10][11]

Differential Diagnosis

The differential diagnoses of anemia include disorders that may present with overlapping clinical features but have distinct underlying mechanisms. Accurate identification of the correct cause is critical for targeted management. In this context, the following conditions must be considered:

• Alpha (α)-thalassemia
• Beta (β)-thalassemia
• Hemolytic anemia
• Aplastic anemia
• Iron deficiency anemia
• Megaloblastic anemia
• Myelophthisic anemia
• Pernicious anemia
• Sickle cell anemia
• Spur cell anemia
• Reduced low-density lipoprotein cholesterol

HBOT should not be given as the first-line treatment without excluding common and reversible causes of anemia. Establishing an accurate differential diagnosis is crucial for effective management and improved clinical outcomes.

Prognosis

Several case reports and series support the effectiveness of HBOT and other “bloodless” modalities in managing both acute and chronic anemia due to blood loss.[12][13][14][15] Although large-scale trials are limited, current data suggest that HBOT can provide sufficient oxygenation in cases of critical anemia when transfusion is not feasible.

Complications

Complications associated with HBOT are rare but can range from mild to severe. Awareness of these potential risks is crucial for maintaining patient safety throughout the treatment process.

Patients may develop mild middle ear barotrauma during HBOT. Although serious complications are rare, potential adverse effects include:

• Eustachian tube dysfunction
• Tympanic membrane rupture
• Oxygen toxicity
• Ear, sinus, or dental pain
• Decompression sickness
• Pneumothorax
• Arterial gas embolism
• Gas embolism affecting the central nervous system, lungs, or joints
• Middle ear hemorrhage
• Hearing loss or deafness
• Visual changes
• Certain hemolytic anemias
• Fire incidents
• Nausea, fatigue, or malaise
• Claustrophobia
• Equipment malfunction [16]

Careful monitoring during HBOT is essential for the early identification and management of potential complications. Preventive strategies, including patient education and individualized pressure adjustments, help reduce risk and promote safe, effective treatment.

Consultations

Involving appropriate specialists is crucial for addressing the underlying cause of anemia, whether it is due to bleeding, hemolysis, or impaired hematopoiesis. Reported adjunctive therapies include polyethylene glycol-conjugated carboxyhemoglobin bovine, hemoglobin-based oxygen carriers, erythropoietin, steroids, and hematinics such as iron, folate, and vitamin B12 (cyanocobalamin).

Many hospitals have liaison committees that work with community-based volunteer Jehovah’s Witness clergy. These volunteers visit patients, assist in developing care plans that honor the patients’ spiritual beliefs, and advocate on their behalf in a respectful and nonconfrontational manner.

Deterrence and Patient Education

Declining a blood transfusion does not mean refusing medical care. Numerous effective strategies are available to treat patients without the need for transfusions. Bloodless medicine and surgery use techniques to minimize blood loss, enhance tolerance to anemia, correct underlying deficiencies, and treat anemia without the need for transfusion.[17]

Pearls and Other Issues

HBOT is generally well-tolerated, and most adverse effects can be minimized with careful patient preparation and planning. The most common adverse event is middle ear barotrauma, which typically presents as ear pain or pressure during compression or decompression of the chamber.[18] This risk can be reduced through slow compression, pressure equalization techniques such as the Valsalva maneuver, and prophylactic use of decongestants such as pseudoephedrine. Sinus, dental, and pulmonary barotraumas are less common but may still occur. Patients should avoid breath-holding during chamber ascent to reduce the risk of pulmonary barotrauma.[19]

Oxygen toxicity seizures are rare and can be minimized by incorporating scheduled air breaks during treatment. Pulmonary oxygen toxicity is also uncommon and may be avoided by allowing adequate intervals, typically several hours, between sessions. Patients with diabetes are at risk of hypoglycemia during HBOT, while those with claustrophobia may experience anxiety due to confinement.[20]

Enhancing Healthcare Team Outcomes

Awareness of HBOT as a treatment option for blood loss anemia remains limited, as does access to facilities equipped to deliver this therapy.[21] Increasing awareness and facilitating transfer to HBOT-capable centers can benefit patients with anemia who refuse blood transfusions. Effective management requires an interprofessional healthcare team, including clinicians, nurse practitioners, physician assistants, respiratory therapists, hyperbaric technicians, hematologists, nurses, and pharmacists. Patients should be clearly informed about the potential risk of death without blood transfusion. Although some patients may benefit from multiple HBOT sessions, the treatment is relatively safe and cost-effective, which is comparable in cost to a unit of packed red blood cells.

Pharmacists play a crucial role in medication reconciliation and monitoring hematinic dosing, which nurses typically administer. Patients opting for treatment without transfusion may encounter skepticism and marginalization. Physicians may feel pressured to provide suboptimal care, which raises ethical challenges and risks. An interprofessional, patient-centered approach enhances both medical and psychological outcomes for patients and their care teams.

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References

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Disclosure: Kelly Johnson-Arbor declares no relevant financial relationships with ineligible companies.

Disclosure: Jeffrey Cooper declares no relevant financial relationships with ineligible companies.