Sickle Cell Information Center Protocols

by James Eckman, M.D. and Allan Platt, PA-C

Acute multiorgan failure syndrome is a severe, life-threatening complication of pain episodes that may occur in patients with otherwise mild sickle cell disease. The syndrome appears to be reversed with prompt, aggressive transfusion therapy. The onset of organ failure was associated with fever,rapid fall in hemoglobin level and platelet count, nonfocal encephalopathy, and rhabdomyolysis. Bacterial cultures are negative in most cases. Aggressive transfusion therapy is associated with survival and with rapid recovery of organ function in most episodes. The syndrome may develop in patients with previously exhibited relatively mild disease with little evidence of chronic organ damage and may be recurrent. High baseline hemoglobin levels may represent a predisposing factor.

Present Illness. Patients with acute multiorgan failure present with pain that is typical in distribution, but it is unusually severe for the patient. Deterioration on the third to fourth hospital day is common of therapy for an acute pain episode.

Past Medical History. Is this pain typical of previous pain episodes? Usually severe pain must alert the clinician to the potential development of this complication. Patients with past episodes of acute chest or acute multiorgan failure may be at higher risk

• Vital signs. Pulse, blood pressure, temperature, respiratory rate and quality (shallow, splinting, labored, retraction, accessory muscle use).
• General. Altered mental status is common at onset.
• HEENT. Increasing jaundice.
• Neck. Nucal rigidity.
• Chest. Check for point tenderness, swelling, erythema, retraction, asymmetry.
• Lungs. Percussion and palpation for dullness, increased resonance, fremitus. Auscultation for rales, wheezes, rhonchi, inspiratory:expiratory ratio, change in breath sounds, E to A. Listen to cough.
• Heart. Neck veins for venous pressure and pulse, point of maximum impulse, thrills, S1, S2, S3, S4, murmur, rubs, edema.
• Abdomen. Bowel sounds, hepatosplenomegaly, tenderness, rebound, masses. Subcostal retractions in child.
• Extremities. Cyanosis, clubbing, edema, calf swelling, calf tenderness, cords, erythema, pulses.
• Neurologic. Mental status, cranial nerves, coordination, muscle strength, sensation.

• Minimum Evaluation. CBC with differential, reticulocyte and platelet count, electrolytes, AST, LDH, Bilirubin total and direct, creatinine, and blood gases. ECG for patient over 30 years old. Chest x-ray. If sputum production is present, do smear and culture.
• Acute multiorgan failure is initially heralded by a fall in hemoglobin and platelet count from baseline. AST,ALT, LDH, direct and total bilirubin and creatinine become elevated.
• Additional Evaluation. If chest x-ray is negative and pulmonary infarction is suspected, consider V/Q lung scan and blood gases. CT or MRI to evaluate mental status changes. Blood cultures if and lumbar puncture if fever is present.

• Acute Multiorgan Failure – Defined as the acute deterioration in function of two of three organ systems: the lung, liver, and kidney. There is often also deterioration in mental status and evidence of rhabdomyolysis. A fall in hemoglobin and platelet count form baseline are early manifestations.
• Acute Chest Syndrome - defined as a new chest infiltrate in a sickle cell patient- Etiologies include pneumonia, pulmonary infarction, bone pain from sickling, bone infarction, and fat embolism.. Differentiation of these disorders can be very difficult and all occur in high frequency in patients with sickle syndromes. Fat embolism, pneumonia, and pulmonary infarction cause pleuritic chest pain, fever, leukocytosis, pulmonary infiltrates, hemoptysis, and hypoxia. Pulmonary infarctions occur de novo without emboli from phlebitis. Pneumonia is more likely in children, with high fever, leukocytosis with left shift. Older children and adults have purulent sputum (younger children swallow theirs). Chest radiograph often reveals a small pleural effusion. Infarction from sickling is more common in adults, with hemoptysis, positive V/Q scan with negative chest x-ray, and in patients without fever or leukocytosis. If in doubt, always treat for pneumonia. Liver tests and creatinine remain normal.
• Drug Overdose - Because of the severity of the pain, the patients are often receiving high doses of narcotics so initial change in mental status may be attributed to overdose of medications. Change in the laboratory parameters notes above and failure to respond to narcan administration support the diagnosis of multiorgan failure.

• Transfusion – All patients require immediate, aggressive transfusion therapy, usually with acute red cell exchange transfusion. Patients with hemoglobin level of > 7g/dl should primarily be treated with erythrocytopheresis or manual red cell exchange. If the hemoglobin level is < 7 g/dl and rapidly falling, simple transfusion of packed red cells to maintain a hemoglobin of 10g/dl may be adequate.
• Support – Intensive medical support is required. Narcan is given as a trial to reverse potential narcotic suppression. Oxygen therapy is indicated for hypoxia with monitoring by frequent blood gases or continuous transcutaneous oximetry. Intubation with mechanical ventilation is often required to maintain adequate oxygenation. Fluids and electrolytes must be used judiciously based on continuous monitoring of input and output and frequent electrolyte determinations. Acute dialysis may be required for volume overload or uncontrollable electrolyte levels.
• Antibiotics - Empiric treatment with antibiotics is indicated after appropriate cultures have been obtained. Third generation cephalosporins with activity against S. pneumoniae and H. influenzae are good initial choices, however, penicillin or ampicillin may be appropriate based on sputum smear findings and local patterns of H. influenzae sensitivity. Empiric addition of a macrolide antibiotic (erythromycin, azithromycin, or clarithromycin) should also be considered because Chlamydia and Mycoplasma infections are common. Antibiotic changes are based on response to therapy and results of cultures and sensitivities.

The prognosis for complete recovery is good if the syndrome is recognized early and treated aggressively with transfusion support. Patients with pain episodes that have unusually severe pain should be monitored closely for the development of acute multiorgan failure. Periodic evaluation of hemoglobin, platelet counts, bilirubin, creatinine, and CPK especially on the thrid or four day of the pain episode may increase early recognition. Alteration in mental status requires prompt, complete evaluation and therapy.

Patients with previous episodes appear to be at increased risk for future episodes. Education must include prompt presentation for evaluation of pain episodes and notifying health professional about past episodes.

Hassell KL, Eckman JR, Lane PA Acute multiorgan failure syndrome: a potentially catastrophiccomplication of severe sickle cell pain episodes. Am J Med 1994 Feb;96(2):155-62

Athanasou NA et al. Vascular Occlusion and Infarction in Sickle Crisis and the Sickle Chest Syndrome J. Clin. Path. 38:659, 1985.

Golden C, et al. Acute chest syndrome and sickle cell disease. Curr Opin Hematol. 1998 Mar; 5(2): 89-92.

Vichinsky EP, et al. Acute chest syndrome in sickle cell disease:clinical presentation and course. Cooperative Study of Sickle Cell Disease. Blood. 1997 Mar 1; 89(5): 1787-1792.

Vichinsky E., Williams R, Das M, Earles AN, Lewis N, Adler A, McQuitty J, Pulmonary fat embolism: a distinct cause of severe acute chest syndrome in sickle cell anemia. Blood, 1994. 83(11): p. 3107-12.

McMahon L., Mark EJ, A 22-year-old man with a sickle cell crisis and sudden death. N Engl J Med, 1997. 337(18): p. 1293-1301.

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Last modified: June 08, 2001