Introduction

Sickle cell anemia is an autosomal recessive disease caused by the substitution of valine for glutamine at the sixth amino acid position of the beta chain of hemoglobin (termed hemoglobin S)₁. Although the manifestations of sickle cell disease (SCD) do not typically necessitate critical care management, several life-threatening complications such as cerebral vascular accidents, acute chest syndrome, severe anemia related to aplastic and splenic sequestration crises, infection, and multiorgan failure may require admission to the intensive care unit. Acute chest syndrome (ACS) consists of a combination of signs and symptoms including dyspnea, chest pain, fever, cough, multifocal pulmonary infiltrates on the chest radiograph, and a raised white cell count₂. It is a form of lung injury that can progress to adult respiratory distress syndrome. It is estimated that half of all patients with sickle cell anemia will develop ACS at least once in their lives. ACS is the most common cause of death and one of the most common causes of hospital admission for patients with SCD₃. ACS is the leading cause of death in adult sickle cell patients, who had no prior evidence of chronic organ damage.

We describe a 17 years-old male with sickle cell disease and ACS who was successfully treated with red cell exchange transfusion.

Case Report

A 17-year-old man with sickle cell disease was admitted to hospital with painful chest, thighs, and generalized abdominal pain. This was his second admission to hospital with pain crisis. Radiographs of the abdomen, thighs and chest were normal. His oxygen saturation was 98% on air. Laboratory tests revealed hemoglobin of 7.7 g/dL, hematocrit of 21%, white blood cell count of 31.300 /mm³, platelet count of 185.000/mm³. Hb S level was 54%. He was treated with intravenous tramadol infusion using a patient controlled analgesia device and intravenous fluids. Over the next 12 hours, his pain was not well controlled, and the patient's respiratory status progressively worsened. Brain confusion with severe hypoxemia (SpO₂ = 85% on room air) developed. He was cyanosed, and widespread crackles and wheezes were heard throughout the chest. He developed tachypnea, pleuritic chest pain, accessory muscle use, nonproductive cough, fever (38.7°C) and a subjective sensation of dyspnea. Repeat chest roentgenogram demonstrated bilateral patchy consolidation and a diagnosis of acute sickle chest syndrome (ACS) was made (Figure 1).

Figure 1

Figure 1: Chest X-ray on admission to the intensive care unit. It shows diffuse bilateral alveolar and interstitial infiltrates with decreased air entry.

While the patient breathed 8 L/min oxygen through a face mask, arterial blood gas values were pH = 7.24; PaCO₂ = 51 mmHg; PaO₂ = 50 mmHg; saturation = 82%; and lactate = 21 mmol/L. A magnetic resonance imaging scan (MRI) of the head were obtained. The MRI showed no evidence of cerebrovascular pathology, particular infarct or hemorrhage. He was transferred to intensive care unit. He was intubated, and ventilated in a bilevel positive airway pressure (BIPAP) mode with peak inspiratory pressure of 28 cm H₂O, end expiratory pressure of 16 cm H₂O, rate of 18, FiO₂ of 0.6 after recruitment manoeuvre was performed with a sustained airway pressure of 45 cmH₂O for 30 second. Arterial blood gas demonstrated a pH of 7.47, PaCO₂ of 35 mmHg, and PaO₂ of 80 mmHg. Treatment with ceftriaxone was initiated after deep tracheal and blood cultures were obtained. Tramadol was given for pain relief. Oliguria and hypotension ensued. Dopamine (10 g/kg/min) and furosemide (2 mg/hour) was administered intravenously. Blood samples and sputum samples obtained by tracheobronchial suction showed no significant bacterial growth, but his C-reactive protein had risen to 150 mg/l and fever sustained, so the antibiotic coverage was broadened to include clarithromycin on the 2 days of intensive care unit. The patient's status continued to deteriorate, and his chest radiograph revealed additional abnormalities including diffuse bilateral alveolar and interstitial infiltrates. Red cell exchange transfusion was made on the 3 days of intensive care unit (with using AS. TEC 204-Fresenius blood cell separator). This procedure was delayed until 3 days because of some technical problems. Our aim is to reduce of the HbS concentration till under 15% and final hematocrit level between 30-33%. We used of total erythrocyte mount for exchange is 4% of body weight (2400 ml) because of hematocrit level is between 20-33%. Postexchange hemoglobin electrophoresis revealed a hemoglobin S of 7%, hemoglobin A1 of 90%, and hematocrit is 31%. We reached to our target levels of hematocrit and HbS in one procedure. Because of this reason, red cell exchange was not performed secondly. During the next 24 hours, FiO₂ was weaned to 45% and arterial blood gas values were pH = 7.47; PaCO₂ = 41 mmHg; PaO₂ = 105 mmHg; saturation = 99.4%; and lactate = 11 mmol/L. Following days, the patient's recovery was complicated by new persistent fevers and acute cholecystitis and gastrointestinal bleeding. Gastric erosions were diagnosed. Enteral nutrition was stopped and omeprazole was administered. Brain functions, other vital parameters, chest x-ray and organ functions were turned to normal after 10 days of erythrocytapheresis (Figure 2). He was extubated without incident. Following laparoscopic cholecystectomy operation due to gallstone, hydroxyurea was started and the patient discharged from the hospital after a further few days.

Figure 2

Figure 2: Chest X-ray obtained 10 day after erythrocytapheresis shows significant improvement.

Discussion

We describe a patient with sickle cell disease who developed acute chest syndrome with respiratory failure and hypoxic encephalopathy despite aggressive medical therapy including positive pressure ventilation. Red cell exchange transfusion resulted in significant improvement in organ function and oxygenation.

Patients with sickle cell anemia frequently develop acute pulmonary complications of their illness including asthma, thromboembolism, and acute chest syndrome₄. Risk factors for ACS include homozygosity for the SS genotype, a low level of fetal hemoglobin, and higher steady state leukocyte and erythrocyte counts₅. Multiple etiologic factors underlie this syndrome, including infection, hypoventilation from various causes, thromboembolism and pulmonary fat embolism caused by bone marrow infarction₆. ACS commonly follows vaso-occlusive crisis or an acute pulmonary infection. The presence of multilobular, or bilateral, infiltrates is associated with a poorer prognosis₁.

Patients with ACS generally characterized with severe hypoxemia. However, both hypoxemia and hypercapnia were observed in our patients. Increased dead space ventilation due to vasooclusion in pulmoner microcirculation and respiratory muscular fatigue because of hyper ventilation may cause hypercapnia. It has been suggested that bone pain can cause atelectasis and can present as ACS₇. The vasooclusive manifestations of sickle cell disease involve a complex and dynamic sequence of events in the microcirculation. Moreover, low oxygen saturation and anemia worsen tissue oxygenation. While respiratory support is enough to oxygen delivery in some cases, additional strategies such as inhaled nitric oxide₈, exchange transfusion, plasma exchange₉ and erythrocytapheresis₁₀ can dramatically improve the management of this life-threatening SCD complication. Pelidis et al.₁₁ reported that despite maximal conventional support, hypoxia might be as severe as treated only with extracorporeal membrane oxygenation. In Our patient, tissue oxygenation did not improve due to effective ventilatory and haemodynamic support. However, PaO₂, blood lactate level and organs functions were turned to normal after erythrocytapheresis. It was suggested that ACS is caused by hypoxia-enhanced in vivo sickle erythrocyte–pulmonary microvessel adhesion₁₁. Because sickle cells were removed from circulation by erythrocytapheresis, the existence of these pulmonary microvascular occlusions may be prevented.

Manual partial exchange transfusion was introduced more than 30 years ago to treat the complications of SCD including priapism, acute chest syndrome, stroke, retinal, bone, splenic, retinal and hepatic infarction₁₁. In these conditions, therapeutic red cell exchange by aphaeresis has an advantage over normal exchange transfusion by being more rapid, acceptable and clinically safe, especially when automated isovolumetric procedures are carried out with a continuous flow apparatus. Moreover it was suggested that early red cell exchange might be a reasonable approach to prevent severe acute complications of SCD₂.

Respiratory infection is a common precipitant of a sickle crisis₇. Ceftriaxone was started for community acquired pneumonia in our patients. However, clarithromycin had to be added to antibiotic therapy. While infection was documented in 30% of cases with ACS, bacteremia was documented only 1.8% of adult patients₆,₇. The two most common organisms detected in patients with ACS were Chlamidia pneumonia and Mycoplasma₂. Hence, administration of broad spectrum antibiotics including a macrolide or quinolone are strongly recommended as first line therapy₇.

In conclusion, early recognition of complications and improvements in supportive care have decreased morbidity and mortality in patients afflicted with this SCD. It was recommended that SCD patients admitted for painful crisis should be considered in the prodromal phase of ACS7. Since ACS may manifest in hours, physicians should have a low threshold for ordering chest radiographs and arterial blood gas analysis for patients admitted with vaso-occlusive crisis. We believe that erythrocytapheresis is an effective treatment method in patients with ACS who are not improved in spite of effective ventilatory and medical support.

Correspondence to

Alper KARARMAZ, MD Dicle University Hospital, Department of Anesthesiology 21280 Diyarbakir Turkey E-mail: alper@dicle.edu.tr Fax: +90 412 24880520