Sickle Cell Disease

Introduction

In providing comprehensive care for patients with SCD, it is vital to have a well-staffed emergency or other acute care facility where patients can receive initial care during acute complications.  The Emergency Departments (ED) or acute care center and its staff are important components of the team that provides care for patients with SCD.  Because of the episodic nature of the complications of SCD, and their potential for rapid deterioration and serious outcome, patients with SCD frequently consult the acute care facilities.  In many instances the ED is the place where the initial diagnosis of SCD is made, usually after a complication.  Often, the ED is where patients and their famlies are first introduced to the medical care of a disease about which they may have little or no knowledge.  The reception and treatment given to these patients and their famlies in the ED to a large extent determine the degree of confidence that they develop in that hospital and its staff.

An ED in a community with a large population of patients with SCD must be prepared to handle the usual and recognize the unusual complications of the disease.  While many of the acute complications of SCD have well defined signs and symptoms, many of them also mimic other conditions.  Conversely, patients with SCD present with the signs and symptoms of other conditions which may mimic typical complications of SCD.  It is important to consider the possibility of the existence of other conditions not related to SCD when patients with SCD present with the signs and symptoms of acute complications.  Patients with SCD vary widely in the manifestations of their disease.  It is important to recognize such individual variation by relying on past medical records, hisory given by family and the patient, and advice from those familiar with the disease.  Like all patients with chronic disease, patients with SCD may know more about how the disease affects them and how they respond to therapy than the treating doctors and nurses.

A.  Diagnosis of Sickle Cell Disease

Do you treat the child for otitis media and send him home, or do you worry that this child may have sickle cell disease and a potentially life-threatening bacterial infection?

In a patient suspected of a serious sickling disorder, diagnostic work should begin in the acute care facility.  Pertinent tests include:

• Complete blood count (CBC) with differential and reticulocyte count
• Hemoglobin levels may be "normal" in SC, S-⁺ thal, and other mild sickling disorders and in young infants with severe forms (SCD-SS, S-⁰ thal).
• The reticulocyte count is usually increased, but in an infant with very little or no anemia, or in a patient who may be undergoing acute red cell aplasia ("aplastic crisis"), it may be low or appear "normal".  The reticulocyte count should be obtained on all known patients with SCD when being evaluated for acute illness; it is the simplest way of assessing the status of erythropoesis in patients with chronic hemolytic anemia.
• The blood smear usually shows sickle forms and target cells.  But, in young patients with high Hgb F, or patients with mild forms of SCD, sickle forms may be rare or absent.
• Sickle Prep

This test should not be used in newborns and babies less than six months of age!   It should not be used to "confirm" findings reported from a newborn screen.
• This common screening test may be a solubility test, a shake test, or a demonstration of sickling on a slide.
• When it is positive, it implies the presence of Hbg S, and should be confirmed with a more definitive test such as Hgb electrophoresis, isoelectric focusing (IEF), or high pressure liquid chromatography (HPLC).  In older children and adults, the Sickle Prep is positive in sickle trait and all clinically benign or severe sickling disorders.
• The sickle prep is negative newborns with SCD and sickle cell trait because of high levels of Hgb F and the relatively low levels of Hgb S.
• In an emergent situation a negative sickle prep in an older child can rule out the possibility of a severe sickling disorder.
(the 15 month old African-American boy with otitis media should be admitted and managed as if he had a form of SCD, if the sickle prep was positive, until definitive tests prove that he has a benign sickling condition).
 
• Hemoglobin Phenotype
• The hemoglobin phenotype can be determined by several methods.  The "classic" and most popular method in clinical laboratories is hemoglobin electrophoresis.  Other methods such as IEF, HPLC, and identification of mutations by DNA analysis are gradually gaining wider use.
• These tests are not generally available on a stat emergency basis.  If the patient must be transfused prior to establishment of the hemoglobin type, 2 mL of (pretransfusion) blood in an EDTA (purple-top) tube should be saved in a refrigerator for later analysis

In most laboratories the electrophoretic method used for hemoglobin identification is cellulose acetate at alkali pH.  Citrate agar gel electrophoresis at acid pH is the usual confirmatory method.

The diagnosis of sickling disorders can be made at birth, and newborn testing has been incorporated into newborn screening programs in many states.  Establishing the diagnosis in the newborn allows education and preventative care, such as penicillin prophylaxis to be instituted prior to the development of potentially fatal complications.  The results of newborn testing are, unfortunately, not available to most families whose children do not have a clinically significant sickling disorder.

Cellulose acetate electrophoresis at pH 8.6 alone may be inadequate for the diagnosis of sickling disorders in neonates because of the high Hgb F level (60-90%).  For neonates, citrate agar gel electrophoresis at acid pH (6.2) allows for better separation of small amounts of Hgb A or S from Hgb F.  IEF and HPLC methods are also used for newborn screening.
 

• The Genotypes of SCD

In the US, there are four common types of SCD:

Genotype	Full Name	Abbreviation	% in US
S/S	Sickle Cell Disease-SS	SCD-SS	65
S/C	Sickle Cell Disease-SC	SCD-SC	25
S/0	Sickle Cell Disease-S 0 thalassemia	SCD-S 0	3
S/+	Sickle Cell Disease-S + thalassemia	SCD-S +	7
Other less common types include SCD-SD, SCD-SOArab.  In addition, any SCD patient may also have alpha thalassemia.

References:

1. Kim, H.C.  Laboratory identification of inherited hemoglobinopathies in children.  Clin Pediatr 20:161-171, March 1981.
2. Newborn Screening for Sickle Cell Disease and Other Hemoglobinopathies.  Pediatr 83(5):Supplement, May 1989.

1.  Overwhelming Infections in Sickle Cell Disease

a.  Bacterial Infection

• This was the leading cause of death in young children with SCD in the US, account for 38% of all deaths in patients under 20 years of age prior to the establishment of penicillin prophylaxis.  Strep. pneumoniae sepsis and meningitis are the most common causes (86%) and H. influenzae is the second major cause (11%) of infection deaths in that age group.

The combination of penicillin prophylaxis and multi-valent pneumococcal vaccination (especially a conjugated vaccine) is expected to decrease the incidence and mortality of pneumococcal bacteremia in children with SCD.
• SCD-SC is generally felt to be a milder disease than SCD-SS.  However, children under 3 years of age with SC have a risk of bacteremia at a rate almost half of those with SCD-SS (Ref #2, below).  In general, children with SCD-SC should be managed with the same degree of caution with regard to infection as those with SCD-SS.
• Children with SCD-S⁰ are considered to be of the same clinical severity as those with SCD-SS.  However, those with S⁺ have the mildest course of the common SCD types.  Their infection risk is probably much less than those with SCD-SS.  However, they end up being managed like the others because of the lack of data on their degree of risk.
• In the first penicillin prophylaxis study (see reference #4, below), 9 or 16 episodes of pneumococcal sepsis were associated with focal infections: pneumonia (5), meningitis (2), and otitis media (2).  It is incorrect to assume that the child with a focus of infection is in less danger of overwhelming sepsis.
• The most important thing to remember about pneumococcal sepsis in young children with SCD is its rapid, overwhelming course.  The 3 deaths in the penicillin study all occurred within 9 hours of onset of symptoms.
• Disseminated intravascular coagulation is a common feature of fatal overwhelming infection in SCD.
• Deaths have resulted in part from delay in the institution of appropriate are caused by lack of prior knowledge of the diagnosis of SCD, failure of parents to recognize or report signs of infection, and failure of medical personnel to apprecite the potential danger.  However, in many instances, the patient simply succumbs due to the overwhelming course of the infection, in spite of appropriate care.

Fever and Infection

Fever is the only reliable indicator of potential infection in patients with SCD.  There are no quick laboratory tests available which can rule out all bacterial infection or pneumococcal infection alone.  All febrile children with SCD may have serious bacterial infection.  Work-up and management should depend on clinical evaluation considering age, specific hemoglobinopathy, and physical examination.

Laboratory studies

• CBC with differential, reticulocyte count, and platelet count.
• Cultures:  Blood and urine; CSF and throat if indicated by clinical evaluation.
• Xrays: Chest x-ray, as indicated.

Acute chest syndrome chould be ruled out in any young child who presents with fever.  Pulmonary symptoms may be minimal or absent.
• CSF culture:  Lumbar puncture should be performed based on clinical judgement.  The younger the child with high fever, the stronger the indication.  In a patient with vertebral pain, a stiff neck may mimic signs of meningitis.  If such a patient also has high fever, it is safer to rule out meningitis with a lumbar puncture.

Management

• Recent developments have resulted in changes in the standards of practice in the management of the child with SCD and fever.
• Traditionally, all such children were admitted for intravenous antibiotics unti bacterial septicemia was ruled out.  The use of the long acting broad spectrum antibiotic, ceftriaxone, for outpatient management of SCD children with fever and who do not look ill is gaining popularity.
• Intravenous broad spectrum antibiotic therapy should be started without delay (in the acute care facility) in young children, especially those under five years of age, suspected of serious infection, after appropriate specimens have been obtained for culture.
• Admit all febrile children with SCD who look ill for intravenous antibiotic therapy until bacterial infection has been ruled out.  Remeber that penicillin-resistant pneumococcus is becoming an increasingly common organism.  Children who look ill should be covered for such organisms until cultures and antibiotic sensitivities prove such coverage unnecessary.

b.  Malaria

Malaria is the leading cause of death in children with SCD in parts of the world where malaria is endemic.  In those parts of the world, prompt diagnosis oand treatment of malaria is a critical part of the management of the febrile child with SCD.  Providers of care for recent immigrants from malarial regions should be aware of the potential danger of malaria in these patients.

References

1. Powers, D.R.  Natural History of sickle cell disease -- the first ten years.  Semin Hematol 12:267 (1975).
2. Zarkowsky, H., et al.  Bacteremia and sickle hemoglobinopathies.  J Pediatr 109:570-585.
3. Gaston, M.H., et al.  Prophylaxis with oral penicillin in children with sickle cell anemia.  A randomized trial.  N Engl J Med 314:1493 (1986).
4. Wilimas, J., et al.  A randomized study of outpatient treatment with ceftriaxone for selected febrile children with sickle cell disease.  N Engl J Med 329:472-6 (1993).
5. Rogers, Z.R., Morrison, et. al.  Outpatient management of febrile illness in infants and young children with sickle cell disease.  J Pediatr 117:736-739 (1990).
6. Norris, C.F., Mahannah, S.R., Smith-Whitley, K, et al.  Pneumococcal colonization in children with sickle cell disease.  J Pediatr 129(6):821-827 (1996).

2.  Acute Chest Syndrome (ACS)

This term has been used to define a relatively common complication of SCD which may be caused by pulmonary infarction, pneumonia or both.  ACS is defined simply as a new pulmonary infiltrate on chest x-ray or lung scan.  It is usually accompanied by chest pain, respiratory distress, fever and pleural effusion.  It is not uncommon for ACS to develop or become apparent in patients who have been admitted for management of other complicationnnnns of SCD, especially painful episodes.

Presentation

• While ACS seldom presents as an emergency, it always has the potential for rapid progression with potentially fatal outcome.
• ACS is often discovered as part of routine evaluation of fever in a child with SCD.
• Patients with extensive pulmonary involvement often present with fever, chest and pleuritic pain, nasal flaring, and abnormal pulmonary auscultation.  There may be rales, rhonchi, and wheezing; often the only abnormality is decreased breath sounds over a particular area.
• Rib infarction may be associated with or may precipitate ACS.
• Patients with pain elsewhere but who show signs of even mild chest discomfort should be evaluated for possible ACS.

Laboratory Studies

• Chest x-ray
• CBC, differential, reticulocyte count
• Periodic measurement of O2 saturation at steady state in patients with SCD is a good idea since it may be a useful tool for the diagnosis and monitoring of the course of ACS.  In a study at CHOP of the Hb-O2 saturation in children with SCD, acutely ill patients with transcutaneous O2 saturation < 96% and a > 3 percentage point decrease from steady state values, had a probability of having or developing ACS [Reference #3, below].
• Patients with moderate respiratory distress deserve arterial blood gas measurements to help determine their need for oxygen and/or transfusion therapy.
• Cultures, as for investigation for bacterial infection.  Assessment for mycoplasmal or chlamydial infection is not done routinely as part of the initial screening but may be useful if easily available.

Management

• ACS is treated first as bacterial pneumonia with broad spectrum antibiotics and oral erythromycin because bacterial infections could potentially be rapidly progressive in SCD patients.
• ACS is also managed as a vaso-occlusive/infarctive process with hydration and analgesics.  The possible role of increased intravenous hydration and narcotic analgesia as contributing factors in the rapid progression of pulmonary infarction often seen in ACS has been suggested; hydration should be kept at reasonable but not necessarily high rates.  A careful balance should be maintained between using analgesics to prevent splinting and permit adequate ventilatory effort, and inducing respiratory depression.
• Even though thrombosis of pulmonary vessels may be involved in ACS, the condition has not been treated wtih thrombolytic or anticoagulant therapy.
• Respiratory distress and documented hypoxia are managed with oxygen therapy and transfusion of relatively fresh, packed, red blood cells (< 5 day old bank blood).
• It is the impression of many clinicians that patients with pulmonary infarction as the primary basis for ACS tend to respond more readily to red cell transfusions than those whose ACS may be due primarily to infection.
• There are preliminary data to suggest a positive role for bronchodilators in the management of ACS.

References

1. Vichinsky, et al.  Causes and outcomes of the acute chest syndrome in sickle cell disease.  NEJM 342:1855-1865 (2000)
2. Castro, O, et al (CSSCD): The acute chest syndrome in sickle cell disease: incidence and risk factors.  Blood 84:643-649 (1994)
3. Rackoff, W.R., Kunkel, N., Asakura, T., Silber, J.H., and Ohene-Frempong, K.  Pulse oximetry and factors associated with hemoglobin desaturation in children with sickle cell disease.  Blood 81:3422-3427 (1993)
4. Vichinsky, E.P., Styles, L.A., Colangelo, L.H., et al.  Acute chest syndrome in sickle cell disease: clinical presentation and course.  Cooperative Study of Sickle Cell Disease.  Blood 89(5):1787-1792 (1997)

3.  Acute Splenic Sequestration (ASS)

ASS is a sudden pooling of large amounts of blood into the spleen leading to acute splenomegaly, profound anemia, and in severe cases, hypovolemic shock.  Death may occur in a few hours.

• ASS also occurs prior to "autoinfarction" of the spleen, that is, in young children (usually less than 3 years old) with severe forms of SCD, but in older children and adults with milder forms such as SCD-SC.  Patients on transfusion or other therapy which may rejuvenate the spleen or delay its infarction can also develop ASS at older age.
• ASS often occurs in association with a viral or bacterial infection.  ASS is also seen in association with malaria in children who may or may not have SCD.
• Typically, ASS resolves within hours or a few days after a blood transfusion.
• ASS may be recurrent ("yo-yo" spleen) or may be slowly progressive in development.
• Splenic sequestration is not always acute.  Splenomegaly associated with more severe anemia than expected for the patient may be evidence of chronic splenic sequestration which presents with other features of chronic hypersplenism.  Such patients may also have recurrent acute exacerbations.

Presentation

• Patients may present with signs of acute circulatory insufficiency such as pallor (check conjunctiva in dark-skinned patients), lethargy, tachypnea, or shock with massive, tender spleens.
• It helps to find out the size of the spleen at the last examination for comparison.  Parents who have been taught to measure the size of the spleen can be helpful to the examiner in determining changes.

Laboratory Studies

• CBC with differential, reticulocyte count, platelet count
• Findings include severe anemia with increased reticulocytes and nucleated RBCs (in contrast with erythroblastopenia); increased WBCs (25,000 - 30,000 range) with a left shift; and decreased platelet count due to hypersplenism.
• Remeber to interpret the results of the CBC correctly in patients with milder forms of SCD such as SCD-SC, whose baseline Hbg level may be close to "normal".  Hgb of 6.5 in a teenager with SCD-SC and enlarged spleen may signify severe sequestration.
• Cultures as indicated.
• Type and crossmatch for blood.

Management

• Prompt restoration of blood volume with plasma expanders is the most important aspect of emergency management.
• Correction of anemia should be approached carefully to avoid potential circulatory overload.  In ASS, the spleen has a tendency to shrink and decrease the volume of the sequestered blood in response to blood transfusion, thereby reducing the degree of anemia.  The goal of initial transfusion should not be to restore the hematocrit (Hct) or Hgb to normal or steady state values, but to prevent shock and heart failure.  Transfusion should be performed in gradual steps:
• For Hct < 12% (Hgb of 4 g/dL), give enough red cells to only double the Hct after the first transfusion.
• After initial transfusion, wait for 3 to 4 hours for circulatory equilibration and check the blood count to establish a new baseline before giving another transfusion.
• Look for shrinkage of the spleen during or following each transfusion, a potential source of volume overload.
• Further management of recurrent ASS may include chronic transfusion therapy in the very young patient in order to avoid splenectomy before four or five years of age, and splenectomy for older children and those in situations where chronic transfusion is impractical.

References

1. Seeler, R.A. and Shwiaki, M.Z.  Acute splenic sequestration (ASSC) in young children with sickle cell anemia.  Clinic Pediatr 11:701-704 (1972).
2. Topley, J.M., et al.  Acute splenic sequestration and hypersplenism in the first five years in homozygous sickle cell disease. Arch Dis Child 56:765 (1981).
3. Pearson, H.A., et al.  Transfusional reversible, functinoal asplenia in young children with sickle cell anemia.  N Engl J Med 283:334 (1970).
4. Michel, B., et al.  A fatal case of acute splenic sequestration in a 53-year old woman with sickle-hemoglobin C disease.  Am J Med 92:97-100 (1992).

4.  Cerebrovascular Accident (CVA)

Cerebrovascular accidents (strokes) are among the leading cause of death and morbidity in children with SCD in the U.S. accounting for 12% of deaths in patients under 20 years of age.  Children with SCD have a risk of stroke approximately 500 times over that of the general childhood population.  In U.S. urban centers with large African-American populations, SCD is the leading cause of stroke in children.  Strokes occur in about 6 % of all patients with SCD with an annual incidence of about 1 in 200 patient (0.5%) but is most common in SCD-SS.   Strokes are broadly classified into two groups, hemorrhagic or thrombotic (infarctive).  In children infarctive strokes are more common.

• Sometimes fatal in children, CVA in patients with SCD requires emergency management for stabilization of vital signs and prevention of progression of neurological damage.  Patients have made dramatic recovery from severe presenting symptoms including coma.
• Most children recover from CVA with no motor deficits.  In the CHOP series, children <5 years of age are more likely to have residual motor deficits after stroke than older patients.  Degree of neuropsychological damage and its recovery following CVA has not been carefully assessed.
• Because CVAs have a high tendency to recur, referral for long term management is essential.

Presentation

Hemiparesis is the most common presenting symptom of CVA.  Patients also present with transient ischemic attacks, cranial nerve palsies, mono- or quadraparesis, coma, or seizures.  Mild transient episodes in young children are probably missed.  A painless limp in a child with SCD may be a sign of a stroke.

Laboratory Studies

• CBC with differential, reticulocyte and platelet count.  Strokes have occurred in patients with severe anemia due to erythroblastopenia (aplastic crisis) and following excessive transfusion.
• PT, PTT
• Cultures, as indicated.  Lumbar puncture should not be performed unless brain imaging reassures against the danger of brain herniation.
• Blood chemistries, electrolytes.
• Type and crossmatch for blood.

Management

• Emergency life support if necessary
• Seizure treatment if necessary
• Hydration: Intravenous hydration alone may reverse neurological symptoms.  Avoid excessive hydration because of the danger of cerebral edema.
• Alert neuroradiology.  Brain imaging studies, where available, are performed as soon as possible after the patient is stabilized to rule out hemorrhage (which may require surgical intervention) and to define the lesion.  Magnetic resonance imaging and angiography (MRI and MRA) may be superior to computerized tomography (CT) in defining the pathology in stroke during the acute period.
• Early simple and/or exchange transfusion may increase oxygen delivery to the ischemic site, help restore neurological function, and reduce the potential for further vaso-occlusion.
• Long term management to rehabilitate the patien and prevent recurrence of stroke is an essential followup to acute care.
• Routine transcranial doppler (TCD) screening of SCD-SS children for evidence of cerebrovascular disease is now part of standard care.  Chronic transfusion therapy is recommended for children with repeatedly abnormal TCDs.

Reference

1. Powars, D., et al.  The natural history of stroke in sickle cell disease.  Am J Med 65:461-471 (1978).
2. Russell, M.O., et al.  Effects of transfusion therapy on arteriographic abnormalities and on recurrence of stroke in sickle cell disease.  Blood 63:162 (1984).
3. Ohene-Frempong, K.  Stroke in sickle cell disease: demographic, clinical and therapeutic considerations.  Semin Hematol 28:213-219 (1991).
4. Adams, R.J., McKie, V.C., Hsu, L., et al.  Prevention of first stroke by transfusions in children with sickle cell anemia and abnormal transcranial Doppler ultrasonography.  N Engl J Med 339:5-11 (1998).

5.  Acute Red Cell Aplasia

Severe anemia due to transient cessation of erythropoesis occurs in all chronic hemolytic diseases.  Such acute erythroblastopenias often associated with infection and B19 parvovirus has been found to be the causative agent in most cases in the U.S. and elsewhere.  Erythroblastosis coupled with the markedly shortened life span of sickle red cells (16-20 days) leads to very severe and life threatening anemia in only a few days.

Presentation

• Patients often present with signs of severe anemia -- pallor, irritability, headache, or lethargy.  Severe constant headache is probably the most common presenting complaint in children old enough to report headache.
• In many cases the condition is discovered during evaluation of a child who has a febrile illness or one with no complaint at a routine visit.

Laboratory Studies

• CBC with differential, reticulocyte count and platelet count.  A low hemoglobin level with low reticulocyte count, usually less than 1%, is a hallmark of so-called "aplastic crisis".  This is in contrast to acute splenic sequestration in which severe anemia is accompanied by an outpouring of young red cells and white cells.
• Cultures, as indicated.
• Type and cross match for blood.

Management

• If the anemia is severe, admit the patent for observation to decide when or whether to transfuse.
• The decision to transfuse should be based first on clinical presentation.  The degree of anemia, reticulocyte count, and if available, the state of erythropoesis in the marrow should be considered in the decision on transfusion.  The goal of initial transfusion is to prevent cardiac failure and shock.
• When transfusing use small aliquots of red cells to prevent circulatory overload.
• B19 parvovirus has been reported to cause first and mid-trimester abortions due to hydrops fetalis.  It is important to isolate patients suspected of aplastic crisis, especially from pregnant women (including caregivers such as doctors, nurses and medical students).

References

1. MacIver, J.E., and Parker-Williams, E.J.  The aplastic crisis in sickle cell anemia.  Lancet 1:1086-1089 (1952).
2. Serjeant, G.R., et al.  Outbreak of aplastic crisis in sickle cell anemia associated with parvovirus-like agent.  Lancet 2:595 (1981).
3. Young, N.  Hematologic and hematopoetic consequences of B19 parvovirus infection.  Semin Hematol 25:159 (1988)

C.  Painful Episodes

Painful episodes are the most common complication of SCD.  This well-known fact not withstanding, patients with SCD presenting with acute pain often meet resistance in receiving adequate attention to their pain.  Part of the reason for such reception is the difficulty in assessing a complication which has no reliable laboratory measurement and often, no objective physical findings.  Painful episodes remain one of the least well-managed complications of SCD.  It is worth remembering that patients do not consult the acute care facility or their doctors in 70% of painful episodes.

In the Cooperative Study of SCD (Ref #1, below), 39% of 3576 SCD patients observed for 18,356 patient-years had no episode of severe pain requiring ED visit or hospitalization; another 40% had less than one painful episode per year, and 1% had more than six episodes per year.  The 5.2% of patients who had 3-10 episodes per year accounted for more than 32.9% of all painful episodes.

The pain is usually in the extremities, ribs, sternum, vertebral column or abdomen.

Patients with recurrent attacks of pain are difficult to manage in the ED; a well-defined plan of management should be developed to avoid inconsistency.

Presentation

• Patients complain of "typical crisis pain".  Older patients can usually distinguish between "crisis pain" and other sources of pain.
• Swelling, erythema, and warmth may or may not be present at the site of the pain.  Do not assume that all pain in a patient with SCD is caused by acute vasoocclusion.  For example, abdominal pain due to cholecystitis has a different set of evaluation and management options.  Also, pain may be due to causes other than those typical of SCD.  It is important to physically establish the source of pain when examining a young child; a limp may be painless (see CVA above) and not necessary a sign of a painful leg.
• Mild to moderate fever is not an uncommon feature of painful episodes.

Laboratory Studies

• CBC with differential, reticulocyte count, platelet count.  Blood counts are usually unchanged from steady state levels in uncomplicated vasooclusive events.
• Cultures, as indicated.
• Chest X-ray as indicated.  Acute chest syndrome is often associated with painful episodes; it should be ruled out in patients with chest pain or fever and pain elsewhere.

Management

The primary goal of management of painful episodes is to alleviate pain and suffering.  Since painful episodes are usually not life-threatening in children, it is important also to reduce the level of anxiety in the patient and family.  The word "crisis" tends to add to the heightened anxiety.

Analgesics

Assess the degree of suffering, and select an appropriate drug and dose based on age and prior history.  Acetaminophen, opioids, and nonsteroidal antiinflamatory drugs (NSAIDS) are the standard medications used in pharmacological management of sickle cell related pain.

Placebos have no place in the management of sickle cell related pain.

Severe to Moderate Pain

• Give opioid analgesic, e.g., Morphine sulfate, 0.15 mg/kg/dose q 3-4 hours IV by infusion over 10-15 minutes or, by subcutaneous injection or intramuscular injection.  IM injections hurt, particularly in children, and lead to muscle sclerosis.


Where available, patient controlled analgesia (PCA) may be a useful and less contentious way of administering opioids to patients who are familiar with its use from prior inpatient management.

Alternative:  Ketorolac (Toradol), 1 mg/kg load, then 0.5 mg/kg q 6 hours.
 

• Also give NSAIDs, e.g., Ibuprofen 10 mg/kg/dose q 6-8 hours PO.  Alternative: Acetaminophen 10 mg/kg/dose po q 4 hours.
• If the pain is relieved for 3-4 hours, give effective PO opioid, e.g:
Hydromorphone: 0.05-0.06 mg/kg/dose q 4 hours or
Oxycodone 5-10 mg/dose q 4 hours (adult) or
Codeine 1 mg/kg/dose q 4 hours
and observe for one hour.
Continue NSAID or acetaminophen.
• If moderate or severe pain returns, repeat the parenteral narcotic dose and observe.
• When pain is under control, resume management with oral opioids, as above.
• If relief is maintained, discharge the patient with a small prescription and referral for follow-up.
• A final dose of parenteral narcotics "for the road" is not recommended.
• If significant pain persists after several hours, admit the patient to the hospital.

Mild Pain

• Give NSAID plus acetaminophen alone or in combination with PO opioid as above.  Aspirin can be given if the child has no symptom of upper respiratory infection.

Note:  prevention of drug addiction should not be the reason to withhold treatment for pain.  Patients have become addicted from medications obtained from outside regular medical channels or from physicians who were too liberal with prescriptions for home use.

Hydration

• Clinical experience suggests that increased hydration may shorten the duration of painful episodes and may make the patent feel more comfortable.
• Increased oral fluids are adequate for children with mild pain.
• Intravenous hydration is appropriate for patients with more severe pain, especially older children and those unable to take increased oral fluids.
• Administer IV (+PO) fluids at 1.5 x maintenance plus losses, if any.
D5 0.22 NaCl (quarter NS) for young children
D5 0.45 NaCl (half HS) for adolescents and adults

Oxygen

• Oxygen therapy serves no useful purpose in non-hypoxic patients; prolonged use may suppress red cell production in the marrow.
• It does not shorten the duration, reverse or decrease the severity of painful episodes