Sickle Cell Disease, “Answers”

 1.)    How do you determine whether or not a sickle cell patient is currently experiencing an acute pain crisis? 

Acute pain crises are one of the most common reasons patients with sickle cell disease (SCD) seek medical attention in the emergency department.  The most common locations SCD patients complain of pain in acute crises are the upper back (63%), left arm (61%), legs (38%), and chest (26%). Episodes can last from 2-7 days (Wilkie, 2010).

The problem, unfortunately, is the widespread belief that exists among  physicians and nurses that opioid addiction and abuse runs rampant within this population.  In a survey of 286 physicians at academic hospitals throughout the US, over 80% of physicians felt that self-reporting was not the most reliable indicator of pain in this patient population (Labbe, 2005).  This often places the emergency physician in a false conundrum: How do I know that my patient is truly experiencing an acute pain crisis versus seeking opioids to feed an addiction?

Some physicians may incorrectly use vital sign abnormalities to attempt to identify the presence of an acute pain crisis; however, no correlation between the two actually exists.  One single-center, retrospective review of 459 SCD patients with acute pain crises found no episodes of hypertension associated with an acute pain crisis (Ernst, 2000).  Another study examining the use of ketoprofen in acute pain crises looked at 66 patient episodes and only found one that included tachycardia (Bartolucci, 2009).

In terms of laboratory data, there is also no correlation with hemoglobin level/reticulocyte count and the presence of an acute pain crisis.  Patients often experience acute pain crises without any drop in their hemoglobin level.  Many large interventional trials among SCD patients report hemoglobin concentrations between 8-10mg/dL in patients experiencing acute pain crises, a level that is similar to the baseline in this patient population (Ballas, 2004 & Bartolucci, 2009).  In fact, there is some evidence to suggest that a lower hemoglobin level portends lower rates of acute pain crises because of lower blood viscosity (Bouchair, 2000).

The bottom line is that there is no combination of clinical or laboratory data that can assist a clinician in determining whether or not a patient is experiencing an acute pain crisis.  Unless there is evidence that a patient does not have SCD, take a patient’s complaint seriously and provide them adequate medication to relieve their pain.

2.)    How do you differentiate an acute pain crisis from pulmonary embolus or acute chest syndrome (ACS)?

In patients with SCD presenting to the emergency department with chest pain, it is important to consider non-SCD-related conditions, such as pulmonary embolus, before attributing pain to SCD.  In SCD patients, the incidence of pulmonary embolism secondary to deep venous thromboembolism (DVT) is similar to non-SCD patients matched by age, sex, and race.  Difficulties arise, however, in diagnosing a PE in patients with SCD as there is often a lack of evidence for DVT and their ventilation-perfusion scans are often abnormal at baseline.  Furthermore, the use of hypertonic intravenous contrast agents commonly used in CT angiography may be unsafe, as it can induce further intravascular sickling and worsen renal insufficiency. Unfortunately, there is little evidence in the literature on how to differentiate between these two diagnoses, beyond that which exists for diagnosing PE in the general population.

It is also vital to consider the diagnosis of acute chest syndrome (ACS) in patients with SCD presenting with acute chest pain, as it is the most frequently reported cause of death in these patients. According to guidelines on sickle cell disease management written by the NIH/National Heart, Lung, and Blood Institute in 2002, the diagnosis is made if a patient with SCD presents with at least two of the following signs/symptoms:

  • Chest pain
  • Fever > 38.5 C (101.3 F)
  • New pulmonary infiltrate on chest x-ray
  • Respiratory symptoms (coughing, wheezing, or shortness of breath)
  • Hypoxemia

Therefore, the evaluation of chest pain in patients with SCD should always include a chest x-ray.  ACS is caused either by infection (especially Chlamydophila pneumonia and Mycoplasma pneumonia), pulmonary infarction from in-situ thrombosis, or fat embolism.  ACS may lead to rapid deterioration in pulmonary status; patients often require ICU-level care.  The cornerstone of treatment resides in administering antibiotics as well as exchange transfusions to increase Hemoglobin A levels to > 70% (NIH/NHLBI, 2002).  

3.)    What do you do for patients once you’ve decided this is an acute pain crisis?  Which lab values are helpful?  Do you provide oxygen and fluids to all your patients in pain crisis? 

Although laboratory data may not assist you in determining whether or not a patient is having an acute pain crisis, they can help you assess the severity of a patient’s disease state as well as identify other emergency states in the sickle cell patient.  As discussed, sickle cell patients maintain a baseline hemoglobin level of approximately 7-10mg/dL and a compensatory reticulocytosis between 5-10%.  An acute drop in their hemoglobin level below their normal baseline may be the first indication of a splenic sequestration crisis (seen in children, primarily), transient red cell aplasia (caused by Parvovirus B19), or hyperhemolytic crisis.  A low reticulocyte count (<1%) may further help pinpoint a transient red cell aplasia, whereas elevated LDH, elevated indirect bilirubin, and decreased haptoglobin levels may be markers for hyperhemolytic crises.

The administration of oxygen to sickle cell patients with acute pain crises is often a reflex we perform upon their arrival in the emergency department.  Some small studies and case reports, however, do demonstrate that giving prolonged supplemental oxygen to non-hypoxic patients with SCD can reduce circulating erythropoietin levels in the body and cause marrow hypoplasia (Embury, 1984 & Lane, 1988).  As a result of these studies, many sickle cell experts recommend providing supplemental oxygen either intermittently or to hypoxic patients only.

In terms of fluids, studies have shown reduced sickling when hypotonic fluids are administered (Clark, 1980). Older evidence also demonstrates an association between excess fluid and atelectasis, a risk factor for acute chest syndrome.  As a result, some clinicians advocate D5 ½ normal saline at a maintenance rate instead of IV fluid boluses of normal saline for all euvolemic patients with sickle cell-related pathologies.

4.)    Which pain medications do you use in patients experiencing an acute pain crisis?

Treatment of pain crises in patients with SCD in the emergency department is primarily accomplished through the use of opiates.  The IV route is preferred due to its predictable pharmacokinetics, but oral and subcutaneous routes may be acceptable if IV access is not available.  Morphine, hydromorphone (dilaudid), and fentanyl are all options for pain control.

The NIH recommends administering opiates by IV push every 15 minutes until a patient’s pain score is reduced by 2 on the “1-10 pain scale” (NIH/NHLBI, 2002). Some studies have shown decreased length of stay in the ED and shorter time to pain relief by using a PCA pump as opposed to bolus doses of opiates (Gonzalez, 1991).  Therefore, if available, consider using a PCA pump even if you suspect the patient will not require admission.

The long-term effects of NSAIDS in patients with SCD are not well-studied.  As some studies show they may be associated with renal injury, especially in children, avoid them.  Similarly, if your department still stocks meperidine, it should be avoided in SCD patients: it is renally cleared, making it unsuitable in a patient population with almost universal renal abnormalities as a result of microvascular infarction (even with normal creatinines).

Both ketamine and magnesium are currently being studied as possible adjunct treatments for patients with acute pain crises.  Low dose ketamine infusions in children may improve pain control and decreased the amount of opioid needed in a pain crisis (Zempsky, 2010).  Magnesium may be associated with a decreased length of stay in patients admitted for acute pain crises.  Further studies are underway to fully evaluate magnesium and ketamine’s incorporation into the management of patients with acute pain crises.   

5.)    Which patients do you admit?  For discharged patients, what is the discharge plan? 

Generally speaking, patients with intractable pain that is not controlled in the emergency department require admission.  The question arises as to what is considered “intractable.”  Some physicians use a cut-off of three IV bolus administrations after which patients are admitted, however no rule can be applied to all patients.  The decision for admission is usually a combined decision between the physician and the patient to evaluate the best method of achieving adequate pain control.

Patients can be discharged home as long as their pain can be controlled by oral medications.  As discussed earlier, pain crises may last between 2-7 days.  Therefore, it is important to inform patients to return to the emergency room if their pain returns to an intolerable level.  Patients should be instructed to avoid situations that may induce pain crises, like cold and dehydration, and to follow-up with their hematologist in the outpatient setting within 2 weeks of discharge.


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