Acute Chest Syndrome

Background
ACS is one of the most common and serious acute complications ofSCD. It is the second most frequent reason for hospitalization in children and adults with SCD and the most common cause of death. Clinically, ACS resembles pneumonia and can develop suddenly or insidiously, during hospitalization for a VOC, or after a surgical procedure, especially one involving the abdomen. ACS occurs with increased frequency in people with asthma or prior ACS events. The clinical, laboratory, and radiographic features of ACS-as well as its management and outcome-were comprehensively assessed in a landmark study performed by the National Acute Chest Syndrome Study Group.
A person with ACS typically has sudden onset of signs and symptoms of lower respiratory tract disease (e.g., some combination of cough, shortness of breath, retractions, rales, etc.) and a new pulmonary infiltrate on chest radiograph. In the early stages of ACS, the clinical manifestations can be subtle. Children usually have fever and upper or middle lobe involvement, whereas adults are often afebrile and present with multilobe disease.
The most common well-defined etiology is infection (e.g., viral, bacterial, chlamydia, or Mycoplasma), but the complication may also result from bone marrow fat embolism, intrapulmonary aggregates of sickled cells, atelectasis, or pulmonary edema. In many cases, the specific cause or inciting factor is not apparent. There are no distinctive laboratory features of ACS, although the hemoglobin concentration often declines sharply below the patient’s baseline value. In brief, what would be considered pneumonia in a person without SCD usually fulfills the criteria for ACS.

People with ACS generally improve within several days but some develop rapid respiratory failure and/or involvement of other organs such as the brain, kidneys, and liver. This latter complication is known as “multisystem organ failure (MSOF)” (see page 50). Treatment of ACS may include broad spectrum antibiotics, supplemental oxygen, bronchodilators, and blood transfusions. Markers of an impending severe course of ACS are multilobe disease, increased work of breathing, inability to maintain oxygen saturation above 95 percent even with supplemental oxygen, and pleural effusions. Exchange transfusion is often necessary in such circumstances. The therapeutic role of corticosteroids and other anti-inflammatory agents is uncertain and requires further study. Repeated episodes of ACS occur in many patients and can contribute to development of chronic lung disease.
ACS during a hospital admission for an acute VOC may be prevented by incentive spirometry every 2-4 hours while awake.

Key Question

Summary of the Evidence
One RCT, 27 observational studies, and 45 case reports described sickle cell-related ACS. The overall quality of evidence was very low for all interventions except the use of opioids.

The single RCT enrolled 38 children and found that dexamethasone compared to placebo decreased the mean hospital stay (from 80 to 47 hours), the need for transfusions (from 47 percent to 9 percent), the number of administered opioid doses (from a mean of 20 to a mean of 2.5), and clinical deterioration (defined as an increase in oxygen requirements and respiratory rate). Participants and investigators were blinded, allocation was concealed, and the study did not report any baseline imbalances. This short-term benefit, however, was not demonstrated to persist when examined by larger observational studies with longer followup. The largest of these studies was done in 2009 and retrospectively evaluated more than 3,000 people (more than
5,000 admissions). After adjustment for propensity scores and hospital case mix, the study demonstrated a significant increase in the length of hospitalization in people who received corticosteroids as part of their ACS management. Other studies showed increased adverse effects related to steroids.
The remaining observational studies described benefits of other therapies for ACS (e.g., supportive treatment including oxygen supplementation, mechanical ventilation, pain management, hydration, antibiotics, and simple or exchange transfusion). The quality of these studies was low due to the noncomparative nature of their design. Studies that evaluated antibiotics did not demonstrate a significant effect on patient-important outcomes.
Multiple observational studies evaluated opiates in ACS. In one, nalbuphine hydrochloride reduced the incidence of ACS compared to morphine (12 percent vs. 29 percent) and also reduced hospital stay.256 In the remaining studies, opiates clearly reduced pain but without other effects on the clinical course of ACS. Transfusion studies in ACS showed conflicting results. In one study, length of hospital stay was similar between simple transfusion and exchange transfusion, and ICU stay was longer in the exchange group (5.6 days vs. 2.6 days). Another study found significant correlation between exchange transfusion and fewer days of hospitalization and oxygen requirement. In these and other transfusion studies, sicker patients were more likely to receive exchange transfusion, which indicates a clear selection bias.

Recommendations

Evaluate people withSCD who develop acute onset of lower respiratory tract disease signs and/or symptoms (cough, shortness of breath, tachypnea, retractions, or wheezing) with or without fever for ACS. This should include a chest x ray and measurement of oxygen saturation by pulse oximetry.
(Consensus-Panel Expertise)
Hospitalize people with ACS.
(Consensus-Panel Expertise)
Treat people with SCD who have ACS with an intravenous cephalosporin, an oral macrolide antibiotic, supplemental oxygen (to maintain oxygen saturation of greater than 95 percent), and close monitoring for bronchospasm, acute anemia, and hypoxemia.
(Strong Recommendation, Low-Quality Evidence)
In people with SCA, give simple blood transfusion (10 mUkg red blood cells) to improve oxygen carrying capacity to people with symptomatic ACS whose hemoglobin concentration is >1.0 g/dl below baseline. If baseline hemoglobin is 9 g/dl or higher, simple blood transfusion may not be required.
(Weak Recommendation, Low-Quality Evidence)
In people with HbSC disease or HbSW-thalassemia with ACS, decisions about transfusion should be made in consultation with an SCD expert.
(Strong Recommendation, Low-Quality Evidence)
In all persons with SCD, perform urgent exchange transfusion-with consultation from hematology, critical care, and/or apheresis specialists-when there is rapid progression of ACS as manifested by oxygen saturation below 90 percent despite supplemental oxygen, increasing respiratory distress, progressive pulmonary infiltrates, and/or decline in hemoglobin concentration despite simple transfusion.
(Strong Recommendation, Low-Quality Evidence)
Encourage use of incentive spirometry while awake.
(Strong Recommendation, Moderate-Quality Evidence)