SICKLE CELL DISEASE
Updated Summer 2018 - By Menachem Spira with Kerry Marrone
Adapted from: https://sites.google.com/site/montepeds2/sicklecelldisease
There are many reasons to admit patients with sickle cell disease. Pain is a hallmark of the disease with vaso-occlusive crises (VOC). Sickle cell patients are also at increased risk of infections and multiorgan dysfunction.
Diagnosis
What to ask in the history:
General SCD history:
What type of sickle cell disease? SS vs. SC vs. Sβ0 vs. Sβ+?
What is their baseline hemoglobin level/reticulocyte count?
General questions:
How many hospital admissions for VOCs?
Ever had a transfusion? If so, when was the last one?
Ever had an exchange transfusion? When?
Ever had an episode of acute chest syndrome (ACS)? If so, how many times?
Ever had an episode of aplastic crisis?
Ever had an episode of splenic sequestration? Any problems with the spleen? Do you still have your spleen?
Ever had an episode of cholelithiasis (gallstones)? Do you have your gallbladder?
Ever had serious infections requiring hospitalization? Strep pneumococcal bacteremia, sepsis, meningitis?
Other complications to ask about: avascular necrosis of the hip, stroke, priapism, osteomyelitis, dactylitis (younger children), hyphema
On chronic transfusion therapy? Candidate for bone marrow transplantation?
SCD healthcare maintenance to check on:
Immunizations
Pneumococcal vaccines (refer to the CDC guidelines for the most updated recommendations)
Conjugate vaccine (PCV13, Prevnar®) per routine childhood schedule (4 doses by 15 months)
Polysaccharide vaccine (PPSV23, Pneumovax®), administered at age 2 and booster at age 5
Generally, administration of PCV13 should precede administration of PPSV23
Meningococcal vaccine - given at age 2 and boosters every 5 years
Influenza vaccine - inactivated vaccine recommended beginning at age 6 months
Medications
Penicillin prophylaxis
Typically initiated when SCD diagnosis is made and continues until at least age 5
Continues for longer if history operative splenectomy, pneumococcal sepsis or other serious complications
Penicillin VK - 125 mg BID until 3, 250 mg BID after age 3
Hydroxyurea
Look at MCV; most compliant patients will have high MCV
Folic Acid - recommended after age 1
Any home medications for chronic pain? e.g. methadone
Is the patient on a PO pain plan?
Screening
Transcranial Dopplers - yearly screening recommended from ages 2 to 16 to evaluate for cerebrovascular accident if normal More frequently if any abnormal findings
Ophthalmologic evaluation - yearly screening recommended starting at age 8 to evaluate for sickle retinopathy
Regular follow-up with a hematologist - every 3-4 months if SS or Sβ0, every 6-12 months for SC or Sβ+
Family History of SCD
Anyone else in the family with sickle cell disease? What types?
What type parents have or are carriers for?
Specific history for chief complaint of pain (VOC)
When was the last crisis?
Triggers? Increased risk of VOC associated with cold exposures, fever, and dehydration
Where is the pain? Is it typical of their usual pain?
How bad is the pain on scale of 1-10?
If multiple locations, assess the pain scale at each site
What pain medications were taken at home prior to presentation?
Type, amount and time of last dose
Any associated fever?
Children with sickle cell disease are at increased risk for serious bacterial infections including septicemia and meningitis particularly from encapsulated bacteria. This is due to the defective splenic function or asplenia which typically begins in the first year of life. According to the NHLBI guidelines, fever in sickle cell is defined as T ≥ 38.5°C (101.3°F). At CHAM, we simplify is to T ≥ 101°F (38.3°C).
Specific history for chief complaint of fever (per NHLBI guidelines
General questions about fever.
When it started, temperature, method of measuring, palliating factors, exacerbating factors, etc
Associated symptoms, localized infection
Otitis: ear pulling, ear pain, discharge
URI symptoms: cough, sneezing, rhinorrhea
Pulmonary symptoms: chest pain, dyspnea, SOB (think ACS)
GI symptoms: diarrhea, vomiting, nausea, abdominal pain
UTI symptoms: burning, frequency, urgency, dysuria
Headache/neck stiffness (meningitis)
Skin lesions, cellulitis, joint pain/stiffness
What to look for on physical exam:
If patient has a fever it is important to look for a source of fever (i.e. AOM, URI sx, septic joint etc.) For suspected VOC, consider physical exam findings associated with localized pain. Some important things to look for on exam in a patient with sickle cell disease are:
Vital signs
Fever? T ≥ 101°F or 38.3°C (rectal temperature in children <24 months)
Pallor of conjunctiva/mucous membranes/nail beds/looks pale? Scleral icterus or jaundiced appearing? Erythematous, bulging TMs?
Presence of a murmur, tachycardia
Respiratory distress, tachypnea, cough, wheezing, flaring/retractions, etc.
Presence of a spleen/splenomegaly? Hepatomegaly? Murphy’s sign?
ulcers/rash, cellulitis
Joint swelling (septic joint) or limb swelling (dactylitis, typically <2 years old), point bony tenderness (osteomyelitis, bony infarct), decrease ROM/pain ROM (AVN)
Initial Tests:
For every patient with SCD
CBC, with differential and reticulocyte count
Type and screen (must be renewed every 3 days)
Obtain consent early for blood products if you anticipate the need for transfusion in the future
For patients with SCD presenting for fever, a comprehensive infectious work is indicated
Blood culture (for every patient)
Chemistry and liver tests
Chest XR if respiratory symptoms (or in any patient with fever T ≥ 38.5°C, 101.3°F)
Urinalysis, urine culture for children <2 years or if s/sx of UTI
Lumbar puncture and CSF culture if meningeal signs
Other tests as appropriate: electrolytes, liver tests, Hgb electrophoresis (if none found in the medical record (Epic) or in anticipation of possible exchange transfusion)
Imaging as dictated by symptomatology: Chest X-ray, lung ultrasound, abdominal ultrasound, hip X-ray, MRI head
Management
Initial steps in the Emergency Department
Stabilize the patient
If patient is in respiratory distress - supplemental O2, incentive spirometry, albuterol every 4-6 hours
Page the on-call Pediatric Heme-Onc Fellow
Pain control in VOC
Pain scales
Infants - FLACC SCALE
3-9 years - ☺ (Wong-Baker) SCALE
9 years and older - Numerical rating scale 1-10
Initial interventions (in ED or Clinic) for patients reporting pain score ≥ 7
Morphine IV/SQ 0.1 mg/kg q3-4hr followed by pain scale assessment 15 min later
If no improvement after 15 min: Give rescue dose of 0.05 mg/kg IV/SQ
Max starting dose: 15 mg/dose, No maximum total dose as long as patient has appropriate respiratory rate and SpO2 >95%
And one of the following:
Ibuprofen: 10 mg/kg PO OR
Ketorolac: 0.5 mg/kg IV (loading dose, max = 30 mg) in Pts with normal BUN/Cr, max 5 days/month If no improvement (pain ≥7), admit
Patients who have failed morphine or have a morphine sensitivity: hydromorphone (Dilaudid) IV/SQ 0.015mg/kg q3-4 hrs. Rescue dose: 0.0075mg/kg at 15 minutes if no improvement (maximum starting dose for opioid naïve patient is 2 mg /dose)
Fever in SCD
Empiric antibiotic therapy
Promptly administer antibiotics in the ED once blood cultures have been collected (do not delay for other cultures or labwork)
3rd generation cephalosporin is preferred:
Ceftriaxone 80 mg/kg/dose IV/IM daily (maximum single dose 2 g)
Consider adding vancomycin for suspected meningitis or in patients who are too hemodynamically unstable for LP (15 mg/kg IV, maximum dose 1 g)
If true cephalosporin allergy, can use clindamycin 10 mg/kg/dose IV every 6-8 hours (maximum dose 900 mg)
Add macrolide (eg, azithromycin or erythromycin) if concurrent ACS
Infectious workup as above
Criteria for admission
Respiratory distress or ACS
Age <2 years in HbSS or HbS-β0 thalassemia (invasive bacterial infection less likely in HbSC or HbS-β+ thalassemia)
Fever >40°C (104°F)
WBC >30,000/microL or <5,000/microL
History of bacteremia
Hgb drop of >2 g/dL from baseline
Cephalosporin allergy
Indwelling central venous lines, PICC lines, or subcutaneously implanted central venous catheters
Signs of systemic toxicity, hemodynamic instability, and/or signs of serious infection such as meningitis
Social: noncompliance or parental concern
Inpatient management
Pain Management for VOC
Start with patient controlled analgesia (PCA) – usually morphine, but can be hydromorphone (Dilaudid)
Morphine bolus: 0.025 mg/kg/dose – maximum initial dose: 2 mg
With 10 min lockout
Hydromorphone bolus: 0.005mg/kg/dose – max initial dose: 0.2 mg
With 8 minute lockout
Continuous (basal) infusion is no longer routinely used
PCA is not used in children younger than 5 years old
The patient must understand the way the PCA works
The parent or other caregivers should not be pushing PCA button for the patient but nurse administered analgesia is an option
Adjuvant medications for pain
NSAIDs
Ketorolac (Toradol)
<60 kg - 0.5 mg/kg/dose IV every 6 hours (maximum single dose: 30 mg)
>60 kg - 30 mg/dose IV every 6 hours
Maximum is 20 doses (5 days) in a 30 day period in patients with normal renal function
Switch to ibuprofen if still requiring analgesia
Ibuprofen (Motrin)
>6 months to <12 years (<50 kg) - 10 mg/kg/dose PO every 6 hours (maximum single dose: 400 mg)
>12 years (<50 kg) - 400 mg/dose PO every 4-6 hours as needed
Acetaminophen - 10-15mg/kg/dose every 4-6 hours (maximum daily dose: 75 mg/kg/day not to exceed 4,000 mg/day)
If pain is not improving:
Can give IV rescue dose of morphine or hydromorphone (twice the bolus dose) and encourage patient to increase the use of demand button
If patient requires > 2 rescue boluses in a 12-hour interval and patient is utilizing demand button appropriately, may increase bolus dose by 20%
If the pain is still not improving, can change lockout to: 8 minutes for morphine and 6 minutes for hydromorphone and encourage use of demand button
Monitoring and transitioning to oral pain medication
Check the medical record (Epic PCA flowsheets) to quantify the patient’s PCA usage
Use PCA flow sheets (linked here) to assess readiness for conversion to PO pain management
Criteria for transitioning to oral pain management
Stable pain scores
Improving function as evidenced by ambulation, appropriate oral intake
On a stable or decreasing opioid dose
Calculated oral opioid equivalent is not greater than weight based dosing!
Oral opioid analgesics should be ordered PRN and wean the intermittent PCA shortly thereafter. Avoid around the clock dosing
Make sure to start oral medications BEFORE stopping IV medications
Patient may receive IV opioid rescue if severe pain and not due for oral medication
Continue non-opioid oral analgesics around the clock
If patient is still requiring frequent doses of the intermittent PCA, their baseline pain is not well controlled, reconsider ability to wean.
Fluids
IV hydration is not recommended in euvolemic patients able to tolerate PO fluids
If euvolemic but unable to tolerate PO fluids, IV hydration can be started maintenance rate
If signs or symptoms of significant dehydration present, correct for hydration but generally avoid boluses
Can wean fluids as patient tolerates PO
Over-hydration can be harmful and lead to ACS. Maintain euvolemia.
Supportive care
Make sure to assess the patient’s GI motility and their need for sennosides (Senna), docusate (Colace), polyethylene glycol (Miralax)
Start famotidine (Pepcid) for GI protection while on NSAIDs
Incentive spirometry
Encourage patients to use frequently as this has been shown to prevent ACS!
Labs during admission
Serial CBC, with differential and reticulocyte counts
Type and screen (must be renewed every 3 days)
Opioid-induced pruritus
Diphenhydramine (Benadryl): 0.5 mg/kg/dose PO every 6 hours as needed for pruritus (max single dose 50mg/dose)
Hydroxyzine (Atarax): 0.5mg/kg/dose q6-8 hr PRN for itching (max 25 mg/dose)
Some evidence for using nalbuphine (off-label) IV, 2.5-5 mg for severe opioid-induced pruritis
Opioid overdose
If respiratory rate <10/min and O2 sat <90% or 5% below baseline and patient unresponsive to non pharmacologic measures (i.e. tactile and verbal stimulation) must consider opioid overdose
Naloxone: 1-2 micrograms/kg/dose IVP PRN q2-3 minutes (max initial dose: 80 micrograms)
Keep patients on continuous pulse oximetry if concern for overdose
Transfusions
Strong-moderate recommendation for transfusion: symptomatic severe ACS, acute splenic sequestration with severe anemia, and stroke (NHLBI)
Weak recommendation for transfusion: symptomatic ACS with decrease Hgb of 1g/dL below baseline (NHLBI)
Moderate recommendation not to transfuse in uncomplicated painful crisis and priapism (NHLBI)
Patients may require a transfusion for a significant decrease from baseline hemoglobin
Respiratory distress can also be alleviated by a transfusion if the patient is anemic
Typically transfuse 10cc/kg or 1 unit (~ 300cc) at a time
5cc/kg for splenic sequestration
Need to ensure you do not overshoot as increased hemoglobin = increased viscosity of blood which puts a patient with sickle cell disease at risk for a stroke
Goal is to not transfuse past hemoglobin of ~10g (assuming patient is not on chronic PRBC transfusions)
Premedicate prior to transfusions with diphenhydramine and acetaminophen
FEVER: Patients with sickle cell anemia are at increased of severe bacterial infection due to reduced or absent splenic function. At CHAM, fever in sickle cell anemia is defined as ≥ 38.3°C or 101°F. Management is the same as for VOC (with pain management as necessary) with the following additions:
Antibiotics
Continue antibiotics until patient remains afebrile >24 hours and blood cultures rule out
Monitoring
A Pediatric Infectious Disease consult is recommended for any patient with a positive blood culture to optimize antibiotic coverage
ACUTE CHEST SYNDROME (ACS)
Acute chest syndrome is a clinical diagnosis defined as:
≥ 1 of the following manifestations: cough, fever, chest pain, tachypnea, dyspnea, sputum production, or new-onset hypoxia
AND:New pulmonary infiltrate on chest X-ray
Add azithromycin in addition to cephalosporin for atypical bacterial coverage (5 days)
Azithromycin 10/mg/kg (max 500 mg) on day 1 and 5/mg/kg (maximum dose 250mg) on days 2-5
Fluids at 2/3 maintenance (max)
Albuterol q4-6h
If the patient has asthma or responds to albuterol.
Incentive spirometry!
If patient has any desaturations, place on continuous pulse oximetry
pRBC transfusions as needed
Exchange transfusions may be required for refractory cases
What to watch out for:
Make sure the patient’s pain is well controlled
If the patient spikes a fever – must draw blood culture
If there is any development of any respiratory symptoms or the patient suddenly requires oxygen to maintain normal oxygen saturations – think ACS.
Sudden onset of abdominal pain – think cholecystitis or splenic sequestration.
New focal neurological finding – think stroke – stat CBC and brain imaging
Low retic count (with low Hb) – think aplastic crisis – check Parvo titers
Warn the staff – anyone who is pregnant should not go in the patient’s room. Place pt. on respiratory isolation
Low platelet count or large drop in Hgb – think splenic/hepatic sequestration
Occurs in younger children (6 mo-3 yr) and is rapid in onset – weakness, pallor, tachycardia, abdominal fullness/pain
Check CBC and transfuse (5cc/kg) to restore intravascular volume if hemoglobin is <5 or if patient is symptomatic
Consider operative splenectomy in the future
PAGE HEME/ONC FELLOW IF ANY CONCERNS!
Discharge
VOC
Patient is getting ready for discharge when their pain has been adequately managed by oral pain medications
Patients should be observed 24 hours on oral medications, have a sickle cell action plan completed in the medical record (Epic) and a pharmacy consult for medication counseling prior to discharge
Fever
Patient should be afebrile for 24 hours and have negative cultures after 48 hours before antibiotics are stopped.
For patients that look well and index of suspicion is low, can give a second 24hr dose of ceftriaxone (to cover for 48 hrs) and send patient home (make sure to follow up cultures!)
If a patient has had a positive blood culture you must have negative cultures documented and the patient should finish a course of antibiotics (as determined by what infection they have).
References:
Hastings, Caroline. The Children’s Hospital Oakland Hematology/Oncology Handbook 1st ed. Philadelphia, Mosby 2002.
Engorn, Branden and Flerlage, Jamie, eds. The Harriet Lane Handbook 20th edition. Philadelphia, Elsevier Saunders, 2014: 309-313
http://www.aafp.org/afp/2000/0301/p1544.html
World Health Organization (WHO) starting dosages for opioid analgesics in opioid-naïve children (1-12 years) - http://www.icpcn.org/downloads/OMS-EMPP-PainTreatmentProject-Maket-Dosing-Card-20120209v4.pdf
https://www.ncbi.nlm.nih.gov/pubmed/25203083?dopt=Abstract&yuaemlib
American Society of Hematology (ASH) guidelines - http://www.hematology.org/Clinicians/Guidelines-Quality/Quick-Ref/3466.aspx
http://onlinelibrary.wiley.com/doi/10.1002/ajh.21315/epdf
National Heart, Lung, and Blood Institute (NHLBI)-sponsored expert panel evidence-based report on management of sickle cell disease can be found at NHLBI 2014 PDF
DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. 902861, Transfusion therapy in sickle cell disease; [updated 2017 Jun 27, cited New York July 24, 2017]; [about 27 screens]. Available from http://www.dynamed.com/login.aspx?direct=true&site=DynaMed&id=902861. Registration and login required.
DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. 907368, Management of acute events of sickle cell disease; [updated 2016 Aug 12, cited New York July 24, 2017]; [about 20 screens]. Available from http://www.dynamed.com/login.aspx?direct=true&site=DynaMed&id=907368. Registration and login required.