Acute chest syndrome in sickle cell disease.

Sickle cell anemia affects approximately 250 million people in the world and is the most common inherited blood disorder in the United States. Two million Americans have the sickle cell gene, and close to 80,000 people in the U.S. are diagnosed with the disease.

Most people at risk for sickle cell disease are descended from ancestors who came from Africa or the Mediterranean basin. The disease occurs in approximately 1 in every 500 African-American births and 1 in every 1,000 Hispanic-American births. One in 12 African-Americans and about one in 100 Hispanic Americans are carriers of the sickle cell gene.

Sickle cell is a complicated disease, and for this discussion we will focus on the acute chest syndrome, or ACS, of sickle cell disease. Adults and children seem to have some variances in their ACS outcomes, so this discussion will focus on children. ACS occurs in children with sickling hemoglobin (HbS) presenting as classic sickle cell hemoglobin (HbSS); however, ACS may also occur in Sickle-thalassemia, and Sickle-hemoglobin C disease (HbSC).

The etiology of ACS is not known, but many investigators have looked at the similarities in laboratory and radiographic data in pediatric patients with sickle cell anemia and acute chest and bone pain. ACS is defined as a new infiltrate in a person diagnosed with sickle cell disease, and this finding is associated with at least one more complaint such as concomitant fever, recent infection and shortness of breath.

In a review of the literature, ACS appeared to be most predominant in children with sickle cell disease, with toddlers and school age children 2 to 4 years of age described as the group most at risk. The presence of fetal hemoglobin (HbF) seems to protect babies and younger children from problems of ACS; as hemoglobin F declined with age, risk for ACS increases.

The National Acute Chest Syndrome study group published the results of a multicenter trial and found that the reason for admission for ACS was often complaint of diffuse pain, including bone pain, chest wall tenderness and sternal pain. Acute chest syndrome is usually accompanied or preceded by pain in the chest or extremities, fever, respiratory distress and/or low oxygen saturation.

Pain may precede radiographic evidence of a new infiltrate, the latter being necessary for the diagnosis of ACS. However, starting therapy prior to radiographic evidence was encouraged. Silvester believed that sickle cell children may be predisposed to exacerbation of asthma, which may result in ACS. Kissoon's review of pediatric emergency care noted that an exacerbation of asthma precipitates ACS, and a rigorous evaluation for the need for aggressive asthma therapy should be considered in an acute presentation of ACS.

Admission findings of ACS patients reveal a complaint of pain, hypoxia, decreasing hemoglobin, pulmonary fat embolism and multilobar pneumonia. Studies of pneumonia in ACS find large numbers of different organisms are responsible for the pneumonia, but community acquired pneumonia is a frequent finding. Crawford reviewed children with sickle cell who underwent elective abdominal surgery and found that ACS occurred in these children, with infiltrates found in the lung segments just superior to the operative site.

Blood transfusions, oxygen, and bronchodilators are the most effective in improving oxygenation. The death rate is 1.8 percent in children and 4.3 percent in adults. Quinn and Buchanan noted that although children were the most likely to develop ACS, they were least likely to die from it. Vichinsky and associates noted that the acute pain felt by the patient probably indicated that a fat embolism "had injured the bone, caused necrosis, and then the embolism would progress to the lung." The vaso-occlusion of small vessels in ribs, sterum, or other bones by sickled hemoglobin may also by itself be responsible for acute pain crisis.

The therapeutic objective of improving oxygenation is critically important in ACS, as the abnormal sickling hemoglobin (HbS) has behaviors well beyond what we learn in school about hemoglobin, its normal response to oxygen in the arterial blood, and hemoglobin's role in tissue oxygenation.

HbS forms strands within the red cell that causes the erythrocyte to be sickled or C-shaped. These abnormal red cells not only function abnormally, but their architecture may cause them to clump within blood vessels and block blood flow, causing vaso-occlusive events that cause the patient to have decreased tissue perfusion, increased hypoxia, ischemia, and possibly tissue necrosis.

The very painful sequaelae of ACS often complicates care of this young patient, as ACS requires morphine and fluid therapy. Most authors warn that these need very careful management as these patients may lose the cough reflex and fail to deep breathe and cough after the opiates. Shallow breathing may correspond to worsening infiltrates and atelectasis.

Ueda noted that if HbS behaved as predicted by it's abnormal Bohr effect, even a mild, transient acidosis would be dangerous for a child in ACS because the right shifted hemoglobin dissociation curve causes a large release of oxygen from red cells, an event that would cause further RBC sickling.5 Barnard and colleagues noted that this cascade of events increased the risk of further erythrocyte sickling and would cause further vasoocclusion, and worsened shunt physiology. This precipitous decline in the status of the patient could be observed in something as simple as atelectasis after a diagnosis of ACS.

Several authors believed that the best way to monitor the success of improved oxygenation in ACS was the arterial blood gas. Blood gas results allow a comparison between the oxygen saturation data, especially a calculated saturation from the blood gas machine with the spectrophotometric/cooximetry analysis that allows you to visualize the agreement (or discrepancy) between the values, and then using the pulse oximeter for trending and follow-up. Calculation of the oxygen content and alveolar arterial gradients is also critical measurements in ACS.

If the hematocrit falls below 30 percent, transfusion of the patient would improve oxygenation. The half-life of the HbS is short-lived (20 to 30 days), and replacement of HbS with normal Hb might prevent the cascade of events that would result in further Hb sickling. Aggressive inspirometry, coughing and deep breathing, and bronchodilators could prevent the atelectasis, infiltrates or lung damage that starts the cascade. Achieving some of these therapies, especially inspirometry in very young children with chest wall pain, could be a challenge to the respiratory therapist. Cautious fluid therapy to maintain blood pressure without fluid overload and pulmonary edema, transfusion with evaluation of rheologic considerations, and pain management with opiates and other agents that reduces pain but does not decrease alveolar ventilation.

Several researchers have tried novel approaches to treat a critically ill ACS patient. Peter Betit, a respiratory therapist working with Weiner's research team, found that inhalation of nitric oxide (NO) improved pain relief scores and decreased morphine use during ACS. Gentile suggested that high frequency oscillatory ventilation (HFOV) was useful in respiratory and ventilatory failure in children with ACS. Modulation of phospholipase and the use of hydroxyurea are both under investigation as treatments for ACS.

Acute chest syndrome is an important topic to understand if you are working with pediatric emergencies. The respiratory therapist can be an important team member on the acute care team in ACS emergencies, and future discussions in this journal will look at improvements made in the care of kids with the multifaceted problems of sickle cell anemia.

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by Douglas Masini, EdD, RPFT, RRT-NPS, AE-C, FAARC 

Douglas Masini is the Department Head/Chair of the Respiratory Therapy Program at Armstrong Atlantic State University in Savannah, GA. He can be reached at [e-mail].