Authors: Kenneth Akapo, OSU MS4 // Dr. Michael Barrie, OSU EM Attending
A 24 year old female with history of sickle cell disease presents with a 6 hours history of widespread pain. The pain is in her lower back but also present within the lower and upper extremities. She also endorses mild shortness of breath although she attributes this to her pain episode. She mentions being seen a week ago due to a similar episode during which she also had new onset headaches associated with blurry vision. During that episode, CT scan was unremarkable. During the current encounter, there was low concern for ischemic stroke. The headaches have persisted until now, however, she no longer endorses changes in vision. She also denies any other focal neurologic symptoms.
Upon initial examination, the patient appeared to be in mild distress. She was mentating well and exhibited no focal neurologic symptoms. She was diffusely tender to palpation although she seemed to exhibit more pain when palpating the lower extremities and back. Breath sounds were clear to auscultation bilaterally, and cardiovascular exam was normal.
Before presenting the case to the senior resident, you consider your differential diagnosis – sickle cell pain crisis, acute chest syndrome (ACS), ischemic stroke, acute coronary syndrome (the other ACS), and heart failure among others.
But what findings would help support or refute a diagnosis of acute chest syndrome? And what is the plan to manage the initial diagnosis and treatment of possible acute chest syndrome?
Acute Chest Syndrome:
Acute chest syndrome (ACS) is the most common cause of death in those patients with sickle cell disease. It is defined as a new infiltrate present on chest radiograph accompanied with variety of symptoms including both respiratory ones such as cough, shortness and breath, as well systemic ones such as fever. Although ACS syndrome typically present is conjunction with vaso-oclusive crises, the clinician should maintain high suspicion for ACS in all sickle cell patients.
ACS has many etiologies including pulmonary infections (the most common causes), emboli (bone marrow, fat), and interestingly, iatrogenic causes such overaggressive hydration resulting in pulmonary edema. Irrespective of the cause, ACS results in a self propagating cycle of hypoxia, and resultant increased sickling, and possible eventual death.
Management of ACS:
Pain control- Narcotic medications are the mainstay of therapy in these instances. It is however important to keep in mind the additional effects of these medications, especially respiratory depression. This could potentially lead to hypoxemia with resultant increase in sickling and worsening of ACS. In general, these patients are on home opioid regimens, and can tolerate large doses of narcotic pain medications. However, be aware that some patients with infrequent pain crisis may not be on home opiates. It is wise to ask the patient what their typical pain medication dose is, and ideally consult your institution’s sickle cell pain management plan for that patient.
Fluid supplementation– Fluids, when administered appropriately play an important role by helping to relieve sickling and prevent hypovolemia. However, fluid overload can result in pulmonary edema thereby worsening the patient’s ACS. Isotonic or hypotonic fluids should be considered.
Oxygen– The patient’s oxygen saturation needs to be above 92%. It is however important to keep in mind that pulse oximetry can underestimate oxygen levels. This is due to the difference in type of hemoglobin found in sickle cell patients. Arterial blood gases which make use of co-oximetry are therefore better suited for accurate measurements. However, in the emergent setting, use of an ABG for this purpose is impractical.
Antibiotics– In spite of ACS’s multiple causes, antibiotic therapy is recommended no matter the etiology. This is especially important in light of the fact that sickle cell patients are more prone to infections from encapsulated organisms. Empiric therapy includes IV Rocephin, or if the patient is well enough to go home oral fluoroquinolones such as Levaquin.
Exchange transfusion therapy The need for transfusion therapy varies depending on the severity of the ACS episode. Modalities include simple transfusions and exchange transfusion with the latter being the preferred method in those with severe ACS such as patients requiring ventilator support, patient suspected of having fat or bone marrow embolism.
Neurologic Stroke Syndromes:
Both ischemic and hemorrhagic stroke are potential manifestations of sickle cell disease. Ischemic strokes are more common and are a result of vessel obstruction due to sickling. It is estimated that approximately 1/10th of patients will become symptomatic from an ischemic stroke by the age of 20 in the instances that their disease remains untreated. Hemorrhagic strokes on the other hand have a lower incidence and present in older patients. The diagnosis is typically a clinical one with patient presenting with new symptoms such as headache (as was seen in our patient) and neurologic deficits which can be focal or non-focal.
An important consideration in the management of ischemic strokes secondary to sickle cell disease is the need for transfusion therapy (although the general management is more extensive). Lowering the percentage of sickle hemoglobin reduces vasooclusion and reverses hypoxemia. Current recommendations include reducing the sickle hemoglobin to less than 30%. Unfortunately, children who suffer from strokes have a high risk of developing recurrent strokes. These patient therefore need chronic transfusion therapy in order to decrease their incidence. Chronic transfusion therapy is also recommended for adults with multiple ischemic attacks. It is nonetheless important to keep in mind that additional therapies such as hydroxyurea play a role in preventing recurrence. Unlikely other embolic or thrombotic ischemic strokes in non-sickle cell patients, tPA is not routinely used in sickle cell patients with ischemic stroke symptoms. Instead, emphasis is on aggressively management of the sickle cell exacerbation.
A chest radiograph did not reveal any opacities in the lungs thereby decreasing the likelihood of acute chest syndrome. In addition, this patient’s headaches were believed to be migraine headaches and did not warrant any additional workup seeing that they had not changed in character since her prior admission.
-It is important to have high suspicion for ACS in all sickle cell patients
-Treatment of ACS is multimodal and includes therapies ranging from oxygenation and hydration to transfusion therapy
-Ischemic strokes are more common than hemorrhagic strokes in sickle cell patients
-Exchange therapy plays an important role in the management of stroke syndromes
- DeBaun MR, Vichinsky, EK. Vasoocclusive pain management in sickle cell disease. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2014.
- Field JJ, Debaun MR. Acute chest syndrome in adults with sickle cell disease. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2014.
- George A. Acute stroke in sickle cell disease. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2014.
- Gladwin MT, Vichinsky E. Pulmonary Complications of Sickle Cell Disease. N Engl J Med. 2008;359(21):2254-2265.
- Hulbert ML, Scothorn DJ, Panepinto JA, et al. Exchange blood transfusion compared with simple transfusion for first overt stroke is associated with a lower risk of subsequent stroke: A retrospective cohort study of 137 children with sickle cell anemia. J Pediatr. 2006;149(5):710-712.
- Kassim AA, Galadanci NA, Pruthi S, DeBaun MR. How i treat and manage strokes in sickle cell disease. Blood. 2015;125(22):3401-3410.
- Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2014;45(7):2160-2236.
- Platt OS, Brambilla DJ, Rosse WF, et al. Mortality In Sickle Cell Disease — Life Expectancy and Risk Factors for Early Death. N Engl J Med. 1994;330(23):1639-1644.
- Tintinalli JE, Stapczynski J, Ma O, Yealy DM, Meckler GD, Cline DM. eds.Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e New York, NY: McGraw-Hill; 2016. http://accessemergencymedicine.mhmedical.com.proxy.lib.ohio-state.edu/content.aspx?bookid=1658§ionid=109381281. Accessed July 15, 2017.