MANAGEMENT AND THERAPY OF SICKLE CELL DISEASE

NIH Publication No. 95-2117, Revised December 1995 (Third Edition) National Institutes of Health, National Heart, Lung, and Blood Institute

Chapter 8--Lung

ACUTE CHEST SYNDROME

Acute chest syndrome is the second most common cause of hospital admission in patients with sickle cell disease and, in some cases, represents a medical emergency. It is an acute illness characterized by new pulmonary infiltrates on the chest x-ray and varying degrees of chest pain, dyspnea, hypoxemia, fever, and prostration. Because x-ray changes may take several days to appear, the diagnosis is commonly recognized as it evolves and not immediately on presentation. The term "acute chest syndrome" is used because a more precise etiology is rarely documented. In adults, acute chest syndrome usually results from pulmonary infarction etiologies such as bacterial or viral infection, fat/bone marrow embolism, intrapulmonary sickling, and emboli of sickled red cells. In children, it is better to assume an infectious etiology. Appropriate cultures and serological tests should always be obtained. Recent bronchoscopy-bronchial lavage data suggest that pulmonary fat embolism occurs in as many as 44 percent of patients with acute chest syndrome. Although the illness is frequently self-limited, particularly when it involves a small area of pulmonary parenchyma, it can rapidly progress and may be fatal. Frequent chest syndrome episodes indicate severe sickle cell disease and predict early mortality in adults.

CLINICAL DIAGNOSIS

Acute chest syndrome can develop as an isolated event or during the course of a painful vaso-occlusive episode. Pleuritic chest pain is the dominant symptom in adults. Fever, cough, and tachypnea are often the only findings in infants and young children. Involvement of the diaphragmatic pleura can result in abdominal pain. True lung pathology must be differentiated from sternal or rib infarction or cholecystitis. Although the pain of acute chest syndrome can mimic angina or myocardial infarction, coronary artery disease is rare in children and young adult patients. Depending on the extent of the pulmonary involvement, physical examination usually shows tachypnea, and there may be signs of pulmonary consolidation, pleural effusion, or occasionally, a pleural friction rub. Alteration in mental status may reflect hypoxemia and/or narcotic effect, but it may also be seen in patients with systemic fat embolization. In severe cases in adults, the patient is often considered to have adult respiratory distress syndrome.

LABORATORY DIAGNOSIS

The chest radiograph of patients with acute chest syndrome shows infiltrates in one or more lobes (66 percent have single lobe involvement). Pleural effusion occurs in 15 percent of the cases. Radiographic studies may be normal or nondiagnostic during the first 2 to 3 days, especially if the patient is dehydrated. Cultures of blood, sputum, or pleural fluid occasionally reveal a bacterial pathogen. Measurement of arterial blood gases rather than ear or pulse oximetry may be necessary for initial assessment of the severity of the illness and for subsequent clinical management. Initial samples should be taken while the patient is breathing room air. Because patients with sickle cell disease may have a low arterial oxygen pressure (pAO2) during the steady state, the interpretation of low oxygen tension can be difficult unless arterial gas measurements have been previously obtained. However, severe hypoxemia (pAO2 below 60 mmHg in an adult or below 70 mmHg in a child) indicates potentially life-threatening disease, particularly if it does not improve with oxygen administration. In patients receiving oxygen by face mask, the severity of the pulmonary process can be assessed by calculating the A-a O2 gradient. If noninvasive oximetry is used to monitor trends, it is most helpful in conjunction with periodic arterial blood gas measurements. Complete blood counts, including reticulocyte counts and leukocyte differential counts, should be obtained serially. An increased neutrophil count above baseline level and a shift to the left suggests a bacterial infection. A falling hematocrit, with or without reticulocytosis, is commonly seen as the syndrome evolves and may contribute to tissue hypoxia. In children, S. pneumoniae is less common as a cause of this syndrome than it was before prophylactic penicillin and the pneumococcal vaccine were used. In most adult cases, no pathogen is isolated. Isolation of mycoplasma or viruses or a rise in antibody titers may help suggest the etiology. A viral etiology is more likely in winter, but mycoplasma are more common in the fall. If sputum or bronchial lavage specimens are obtained, they should be stained for fat. A positive result suggests fat embolism. Lung scans generally are not useful in diagnosing the etiology of acute chest syndrome or in making a therapeutic decision. Due to the hypertonicity of most contrast dyes, pulmonary angiography carries the theoretical risk of increased sickling; therefore, the procedure is rarely indicated.

Causes of "Chest Syndrome"

Hemoglobin S related a. Direct consequence i. Pulmonary infarction - in situ sickling aa. etiology unknown bb. hypoventilation 2o to (i) rib/sternal infarction (ii) narcotic administration (iii) postoperative atelectasis. ii. Embolism infarction aa. necrotic bone marrow/fat bb. sickled cells from distal site (i.e., liver sinuoids). iii. Pulmonary edema 2o to fluid overload. b. Indirect consequence-infection i. Bacterial ii. Viral iii. Fungal iv. Protozoan 2. Unrelated to Hb S a. Thromboembolism (from thrombosed vein) b. Opportunistic infection related to HIV infection c. Bronchial obstruction 2o to foreign body or neoplasm d. Acute sarcoidosis e. Other: aspiration, trauma, etc. Treatment All patients with acute chest syndrome must be admitted to the hospital. Depending on the extent of lung involvement and respiratory distress, the intensive care unit may be required for appropriate monitoring of a rapidly changing clinical state. Analgesics should be administered; however, narcotic-induced hypoventilation must be avoided. A delicate balance must be found to provide pain relief and eliminate splinting without causing hypoventilation. Overhydration may be as dangerous as dehydration, and intravenous fluids must be cautiously administered. Oxygen therapy is indicated for hypoxemia, tachycardia, and tachypnea, and it should be monitored by frequent measurement of arterial blood gases. Patients may become profoundly hypoxic if they remove their oxygen masks for eating or bathing. Nasal prongs may be used in these instances, but the amount of oxygen actually inspired will be lower than with a face mask. It is often impossible to make a reliable a priori differentiation between pulmonary infarction and bacterial pneumonia. In 2 to 5 percent of the cases, acute chest syndrome is associated with a positive blood culture; the most common isolates are S. pneumoniae and H. influenzae. Depending on the local susceptibility pattern of these organisms, and whether the patient was on prophylactic penicillin, an appropriate combination of penicillin, cephalosporin, or vancomycin should be used. Oral eryth- romycin should be added if Mycoplasma pneumonia is suspected. Adjustment of the antibiotic regimen will depend on the results of the bacterial cultures. Exchange transfusions should be performed if the patient develops multiple lobe involvement, rapidly progressing disease, or signs of respiratory insufficiency (pAO2 below 60 mmHg in an adult or below 70 mmHg in a child while breathing oxygen) (see Chapter 10, Transfusion). Patients with chronic hypoxemia, as determined by baseline studies, should be considered for exchange transfusions when there is a drop greater than 25 percent from the steady-state pAO2. If progressive severe anemia develops in a patient with borderline abnormal pulmonary function, a simple transfusion of packed red blood cells may be required. Unless thromboembolism is proved, anticoagulant therapy is not recommended.

SYSTEMIC FAT EMBOLIZATION SYNDROME

Systemic fat embolization syndrome is a rare, but often fatal, complication that is due to widespread embolization of liquified necrotic bone marrow fat into the pulmonary vessels and then to the systemic circulation (see Stroke, Chapter 9). Patients with sickle cell disease can develop the syndrome during a severe vaso-occlusive episode. Symptoms include bone pain, fever, chest pain, dyspnea, confusion, agitation, and coma, with or without acute renal failure. In some cases, disseminated intravascular coagulation with severe microangiopathic hemolytic anemia and multiorgan failure can occur. A high index of suspicion is essential for early diagnosis. Pulmonary fat embolization can be detected by the finding of intracellular lipid in secretions obtained by bronchial lavage. Demonstration of necrosis on marrow aspirates, presence of refractile bodies on fundoscopic examination, head and neck petechiae, and fat globules in the urine can be helpful in establishing the diagnosis. If the diagnosis is suspected, early institution of exchange transfusions accompanied by supportive treatment may be lifesaving.

ASTHMA

Asthma and chronic asthmatic bronchitis pose a potential therapeutic problem in sickle cell disease patients. Epinephrine use is associated with increasing heart rate and can compromise cardiac stroke output. The diuretic action of some bronchodilators may dehydrate the patient, but these agents are usually required. Hydration is essential, and intravenous fluids should be administered early during an asthma attack that does not quickly resolve. Long-term management is not different from that for individuals without sickle cell disease.

CHRONIC RESTRICTIVE LUNG DISEASE

Chronic restrictive lung disease, with pulmonary hypertension and cor pulmonale in late stages, is a consequence of previous vaso-occlusive episodes and has a poor prognosis. Diagnosis before the clinical onset of cor pulmonale is based on abnormal pulmonary function tests, chest radiograph demonstrating increased parenchymal markings or fibrosis, and chronic hypoxia. Repeated episodes of midline, severe, crushing chest pain signal myocardial ischemia (without coronary artery disease). With recurrent episodes of acute chest syndrome, the patient develops pulmonary hypertension and heart failure. A chronic transfusion program may reduce the frequency of recurrent attacks of chest syndrome, and nocturnal oxygen therapy may be helpful in selected patients.

BIBLIOGRAPHY

Bellet P, Kalinyak K, Shakla S, et al. Incentive spirometry to prevent acute pulmonary complication in sickle cell disease. N Engl J Med 1995;333:699-703.

Bhalla M, Abboud MR, McLoud TC, et al. Acute chest syndrome in sickle cell disease: CT evidence of microvascular occlusion. Radiology 1993;187:45-9.

Castro O, Brambilla DJ, Thorington B, et al. The acute chest syndrome in sickle cell disease: incidence and risk factors. The Cooperative Study of Sickle Cell Disease. Blood 1994;84:643-9.

Gelfand MJ, Daya SA, Rucknagel DL, et al. Simultaneous occurrence of rib infarction and pulmonary infiltrates in sickle cell disease patients with acute chest syndrome. J Nuclear Med 1993;34:614-8.

Johnson CS, Verdegem TD. Pulmonary complications of sickle cell disease. Semin Resp Med 1988;9:287-96.

Powars D, Weidman JA, Odom-Maryon T, Niland JC, Johnson C. Sickle cell chronic lung disease: prior morbidity and the risk of pulmonary failure. Medicine 1988;67:66-76.

Sprinkle RH, Cole T, Smith S, Buchanan GR. Acute chest syndrome in children with sickle cell disease. A retrospective analysis of 100 hospitalized cases. Am J Pediatr Hematol Oncol 1986;8:105-10.

Vichinsky E, Williams R, Das M, et al. Pulmonary fat embolism: a distinct cause of severe acute chest syndrome in sickle cell anemia. Blood 1994;83:3107-12.

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