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 administered to anemic patients who are symptomatic, to relieve the signs and symptoms of oxygen debt. However, some patients are unable to receive blood transfusions due to religious beliefs or for medical reasons. In these patient populations, hyperbaric oxygen therapy can be administered to increase oxygen delivery to tissues and relieve the signs and symptoms of oxygen debt.
According to the Jehovah’s Witnesses religion, portions of the Bible (including Genesis, Leviticus, and Acts) state that its followers must abstain from receiving blood. Jehovah’s Witnesses will not accept blood transfusions, and this religious belief has been upheld in the American legal system.
Other 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 of morbidity and death after acute and unexpected blood loss from conditions including postpartum bleeding, trauma, and intraoperative hemorrhage.
Up to 1000 Jehovah's Witnesses die each year due to their refusal to accept a blood transfusion. Anemic patients who are elderly, obese, who are on hemodialysis, or who have underlying heart disease are at increased risk for mortality.
The amount of oxygen delivered to the body (DO2) is dependent on the arterial oxygen content (CaO2) and cardiac index (CI). The equation representing this is as follows:
The arterial oxygen content is mostly dependent on hemoglobin concentration; each hemoglobin molecule can carry up to 1.38 ml of oxygen per gram of hemoglobin. A tiny 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 following equation represents the arterial oxygen content:
Oxygen that is delivered to tissues is then extracted and used by the tissues. On average, the human body extracts 5% to 6% volume of oxygen from the blood. 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.
In 1959, the Dutch surgeon Boerema published “Life Without Blood,” a manuscript detailing the use of hyperbaric oxygen therapy (HBO) for the treatment of anemia. 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 which 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 could 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 2000 mmHg. Under hyperbaric conditions, oxygen dissolved in the plasma can approximate or meet the body’s metabolic demands of oxygen extraction. At a treatment depth of 3 ATA, the plasma dissolved oxygen approximates 6% volume, equal to the body’s oxygen extraction.
The patient may be light headed and confused.
Patient evaluation should focus on signs and symptoms of decreased oxygen delivery to tissues. Vital signs may show tachycardia and hypotension. The patient’s mental status may be altered; cerebral infarcts may occur secondary to decreased oxygen delivery to the brain. Ischemic changes may be present on electrocardiography, and decreased urine output may be present due to hypoperfusion. Laboratory studies may reveal metabolic acidosis, abnormal cardiac enzymes, or a base deficit.
The physiologic effects of hyperbaric oxygen therapy in anemic patients are short-lived; the elevated tissue partial pressures of oxygen last only minutes to hours after each hyperbaric exposure. The frequency of hyperbaric oxygen therapy should, therefore, be tailored to the patient’s clinical status. Patients who are more symptomatic may require treatments administered two or three times daily. Treatments can be administered in a monoplace (which holds a single person) or multiplace (which can accommodate multiple people) hyperbaric chamber. Treatment depths are variable and dependent on the individual hyperbaric unit’s clinical procedures, but increased treatment depths will result in higher partial pressures of oxygen and likely increase relief of the symptoms of oxygen debt. Other modalities which can reduce oxygen consumption, including sedation, neuromuscular paralysis, and cooling, can also be utilized as adjunctive therapy. Blood should be minimized whenever possible; pediatric tubes can be used for phlebotomy to minimize unnecessary blood loss. Consultation with a bloodless medicine specialist for recommendations for the use of iron supplementation and erythropoietin may also be considered.
Hyperbaric oxygen therapy is generally well tolerated, and most of the side effects can be minimized by careful patient preparation and planning. The most common adverse event associated with hyperbaric oxygen therapy is middle ear barotrauma, which manifests as pain or pressure in the ears during chamber compression or decompression. Slow compression, use of pressure reduction maneuvers (such as the Valsalva maneuver), and prophylactic administration of decongestants (such as pseudoephedrine) can reduce the risk of ear barotrauma. Sinus, dental, and pulmonary barotraumas may also occur but are rarely encountered in clinical practice. Patients should avoid holding their breath during chamber ascent to reduce the risk of pulmonary barotrauma. Oxygen toxicity seizures are rare and may be minimized by the use of scheduled air breaks. Pulmonary oxygen toxicity is also rare and may be minimized by maintaining well-defined intervals of several hours between each hyperbaric treatment. Patients with diabetes may experience hypoglycemia during hyperbaric treatments, and patients with a history of claustrophobia may experience confinement anxiety.
Anemic patients who refuse blood transfusions should be managed by an interprofessional team that includes nurse practitioners. Patients should be educated that without blood, there is a potential for death. Some of these patients may benefit from HBO therapy, but this requires multiple sessions. The increase in oxygenation is not always assured or consistent with HBO therapy. However, the treatment is relatively safe.
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