Download Pain, Fever, and ACS in Sickle Cell Disease

Pain, Fever, and ACS in Sickle
Cell Disease
Sirish Palle, M.D.
July 26, 2011
Adenine to thymidine at codon 6
in beta Hb on Chromosome 11 leads
to substitution of glutamic acid by valine
Identification
Alabama newborn screen tests for sickle
cell disease
If a screen is positive, order Hb electrophoresis
for verification
If a child has trait, counsel the family regarding
risk in future children
Check Hb electrophoresis at one year old
Newborns
If diagnosed with sickle cell disease:
 Start prophylactic PCN VK at 125 mg PO BID
before 2 months old to decrease risk of death
from pneumococcal infection
Refer to Hematology, refer family to Genetics
for counseling
Give Prevnar (pneumococcal conjugate
vaccine) at 2, 4 and 6 mos old
Give influenza vaccine at starting at 6 mos
Infants and Toddlers
 Start Folic Acid 1 mg PO daily by one year old
 Give Prevnar (conjugate) at 15 mos
 Give Pneumovax (polysaccharide) at 2 yo & 5 yo
 Those that have already received their 4 doses
of Prevnar 7, get additional dose of Prevnar 13
 Continue to vaccinate yearly against influenza
 At 3 yo, change to PCN VK 250 mg PO BID
 May stop PCN VK at 5 yo
 ≤16yo need TCD to assess for risk of CVA and
need for chronic transfusion to prevent
Outcomes
 Severity is generally based on Hb variant:
SS > S-betao thalassemia > S-beta+ thalassemia > SC
 Median life expectancy for HbSS is 45 years, for
HbSC is 65 years
 High WBC, low Hb (<7), and VOC crisis in the
first year of life are the known risk factors for
severe morbidity
Vaso-Occlusive Crises
AKA Pain Crisis
VOC (Vaso-Occlusive Crisis)
Triggers:
Infection
Temperature extremes
Dehydration
Stress
Idiopathic
History to obtain
Location of pain, severity on 0/10 scale
Is this their typical pain or is it different?
Do they have significant headache (worry
about stroke)?
Do they have SOB, chest pain, cough
(worry about ACS)?
If they are male, do they have priapism?
Do they have a fever (worry about ACS,
sepsis, osteomyelitis)?
Labs to order
CBC with differential
Don’t be surprised if the WBC count is elevated
due to stress response
Reticulocyte count
Expect it to be elevated
Chem 14
Therapies
Hydration: D5 ½ NS with 20 meq KCl/L to
run at 150% maintenance
(unless concerns for ACS or for long periods of time)
Heating packs
PT consult for ROM, TENS unit, whirlpool
Encourage OOB, incentive spirometry
Oral Pain Medications
Acetaminophen with Codeine: 120 mg/12
mg/5 mL; 0.5 mg/kg/dose of codeine PO Q
4-6 hours; max dose 60 mg codeine per
dose; watch acetaminophen component
Acetaminophen/Hydrocodone (Lortab):
500 mg/7.5 mg/15 mL; dose depends on
weight, from 3.75 mL to 15 mL PO Q 4-6
hours; watch acetaminophen component
Parenteral Pain Medications
Ketorolac (Toradol): NSAID
0.5mg/kg IV/IM Q6 hours, max dose 30 mg IM,
15 mg IV for pediatrics
Don’t use if concerns for bleeding
Don’t use with other NSAIDS
Caution if renal impairment
Watch for gastric irritation
Use for 5 days only
Parenteral Pain Medications
Nalbuphine (Nubain): opioid
agonist/antagonist
0.1-0.3 mg/kg/dose IV Q 2-4 hours
Max dose 20 mg
Monitor for respiratory depression
Good for patients who have pruritis with
morphine
Morphine
Parenteral
0.1-0.2 mg/kg/dose SC/IM/IV Q2-4 hours
Max dose 15 mg
Can give via PCA if 5 years or older, depends
on child’s maturity
Counsel family that they cannot push the button! This
counteracts the built in safety of a PCA.
Morphine
Oral
MS Contin (extended release)
0.3-0.6 mg/kg PO Q 12 hours
Don’t chew
Comes as 15,30,60 mg
MSIR (immediate release)
0.2-0.5 mg/kg PO Q 4-6 hours PRN severe pain
Comes as 15 mg, 30 mg pills, or as 10 mg/5mL, 20
mg/10 mL solution
Transition from IV to PO Morphine
Oral dose is 3x the IV dose
If a patient is comfortable on Morphine 3 mg IV
Q 3 hours, total daily dose is 24 mg/day
Oral dose = 3 x 24 = 72 mg/day
Can give MS Contin 30 mg PO Q12 hours
Can give MSIR for breakthrough pain; 3-5 mg
PO Q 4-6 hours PRN severe pain
Other Medications
 If patient is on hydroxyurea at home, continue it
at the same dose
 Folate 1 mg PO daily
 Consider transfusion in the case of severe
anemia; typically not done in VOC unless acute
chest, risk of stroke, acute multi-organ failure,
heart failure, reticulocytopenia (eg ParvoB19),
hepatic/splenic sequestration or preoperative
Fever
Fever
 Functional asplenia from sickling in the
microcirculation in 90% of patients by age 6
years
unless chronic transfusions which may prolong the
function of the spleen
 Increased risk of infection with encapsulated
organisms
 Haemophilus influenzae type b
 Streptococcus pneumoniae
 Salmonella typhi
 Neisseria meningitides
 Group B streptococcus
 Klebsiella pneumoniae
Bottom Line
Any patient with sickle cell disease
and T>101 F (38.4 C) gets parenteral
antibiotics, even if you have a source!
Labs that you must have
CBC with differential
Reticulocyte count
CRP
Blood culture
Chest X-ray
Labs that you might want
CP14
UA, urine culture
Parvovirus B19 titers if a drop in Hb and
inappropriately low reticulocyte count
Look for elevated IgM, if +, needs isolation from
pregnant women
If swollen painful limb, consider
osteomyelitis (MRI)
Medications
 Ceftriaxone (Rocephin):
 50-75 mg/kg/day IV divided Q12-24 hours
 75-100 mg/kg/day IV divided Q12-24 hours if cephalosporin resistant S
pneumo suspected/prevalent in area
 Vancomycin:
 Consider adding if clinically ill
 Commonly used vancomycin doses outside of the neonatal period
range from 40 to 60 mg/kg/d divided every 6 to 8 hours
 The exact dose will depend on the clinical presentation and may need to
be altered based on the results of therapeutic monitoring
 Level prior to 5th dose – trough
 Some evidence suggests that keeping vancomycin trough levels >10
μg/mL may help prevent the development of heteroresistance in MRSA,
level closer to 15-20 in CNS, bone/joint infections and/or suspected
MRSA pulmonary infections 
Pediatric Infectious Disease Journal:
May 2010 - Volume 29 - Issue 5 - pp 462-464
Adjusting Vancomycin
 Overall, nephrotoxicity in adult patients is estimated to be <5%
 However, there are reports of an increased risk of nephrotoxicity
when vancomycin is combined with an aminoglycoside
 Use with caution in renal insufficiency (BUN/Creat) & GFR
 Although initially reported to be associated with ototoxicity, this
association has been called into question
 Many initial reports of ototoxicity occurred in patients with potential
confounding factors (eg, concurrent meningitis and aminoglycoside
use)
 Red Man's Syndrome an association of erythema and flushing of
the face, neck, and torso occurs in a significant number of patients
(up to 50% in some series) and is believed to be secondary to
histamine release
 stop/slow infusion rate and administer Benadryl
Other Medications
Hydroxyurea:
Continue at the patient’s home dose
Hold if leukopenia, neutropenia, or
thrombocytopenia is noted
Folate 1 mg PO daily
Acute Chest Syndrome
AKA new infiltrate on CXR and a
fever
Acute Chest Syndrome
 Definition is debated…
 New infiltrate on CXR (the best film is an old film) AND one or
more of the following:
 Fever (>38.5)
 Chest pain
 Tachypnea, wheezing, cough or appearance of increased work
of breathing (retractions)
 Hypoxemia relative to baseline measurements
 Bottom Line: keep ACS forefront in your mind if your
patient has any pulmonary complaints: cough, SOB,
chest pain, chest wall pain, hypoxia on exam
 Febrile pt with SCD need xray up to 61% not clinically suspected
prior to radiograph evidence of infiltrate
 Repeat CXR on kids in VOC pain crisis if resp symptoms
Treatment
 Incentive spirometry with older patients (10
breaths per hour while awake) or have younger
children blow bubbles
 Albuterol nebulizer/MDI Q 4 hours ATC
 Chest PT, Mucomyst nebs
 Ceftriaxone IV or other 3rd generation Cephalosporin
 (consider S pneumo resistance)
 Azithromycin
10mg/kg PO/IV day one, then 5 mg/kg daily for days 2-5
 Continue Folate and Hydroxyurea
Treatment
When should you give oxygen?
When your patient has desaturations <90-92%
Starting oxygen when not needed ( for
“comfort”) can decrease reticulocytosis
If you have to start oxygen, get an ABG first
unless oxygen need is urgent
Keep O2 Sats <95% once O2 started
Treatment
 When should you give blood?
Keep H/H around 10/30
Transfuse with leukocyte poor, sickle trait negative
PRBCs; consider extended antigen match in chronic
transfusion patients to avoid alloimmunization
premedicate with Tylenol and Benadryl
Do not transfuse to >12/36 as this can increase the risk
for stroke
Consider exchange transfusion if worsening even with
H/H 10/30
 Need double lumen central line; Red Cross involved
Consent for Blood
Hydration Status
Overhydration can worsen ACS
If dehydrated, correct with isotonic solution
D5 ½ NS with 20 meq KCl/L at 100%
maintenance for continued fluid needs
Daily weights
Monitor in and outs closely
Adjust fluids as needs
Furosemide if fluid overload suspected
Remember…
Children with sickle cell disease and acute
chest syndrome can get ill very quickly
and go into respiratory failure
When called to evaluate children with
sickle cell disease with shortness of
breath, ALWAYS go to the bedside to
assess them
Case 1
Kevin is a 13 yo AAM with Hb SS disease
who is admitted with left leg pain for the
last 2 days, unresponsive to Lortab 5mg at
home. Pain is 7/10, nonradiating, and is
similar to previous pain crises.
History
What further questions?
Fever?
SOB? Cough?
Priapism?
HA?
Injury or wounds?
PE
Well developed, NAD, mild scleral icterus
T=99, HR=80, RR=16, BP 110/70, O2 sats
97% RA
1/6 SEM
Leg without erythema or wounds, mild
TTP, CR brisk
Labs
H/H 10/30
Retic count 5%
CP14 with T bili mildly elevated
What medications?
He weighs 45 kg and has no allergies
What else do you want to order to treat the
pt in the hospital?
Hospital course
Hospital Day # 2: You are called at 0200;
his leg pain is 2/10 but he has abdominal
pain.
What do you want to do?
Hospital Day # 3: his pain is 2/10 and he is
tolerating food well.
What do you want to do?
Hospital Course
His leg and abdominal pain resolves and
you discharge him home.
What advice should you give his parents?
Importance of yearly influenza vaccine
Importance of fever
Folate 1 mg PO daily
Pain management and concerns for addiction
Case 2
Alexis is a 2 yo AAF with HbSS disease
who comes to your office as a new patient
with T=102. Her parents report that she
has had rhinorrhea for 3 days and has
been pulling at her left ear. She has been
eating and drinking well and has normal
UOP. You examine her and diagnose left
otitis media.
What do you want to do?
Admit her to the hospital
Labs?
Medications? She weighs 15 kg and has
no allergies.
On call
You are paged at 0100 on hospital day #2.
Alexis has vomited once and her parents
say that she is not acting right. The nurse
reports that she seems a little sleepy, but it
is past her bedtime.
What do you do?
In her room…
You find Alexis to be sleepy but awakes
easily. She is fussy when you awaken her
and is somewhat consolable by her
mother. T=104.3, BP is 85/50, O2
sats=100% RA, RR=30. PE: CR is 2-3
seconds, lungs are clear.
What do you do?
Follow-up
A nurse calls you with Alexis’s Vancomycin
level of 14 at 2100 the next night. She is
worried.
What do you do?
What if the level was 22?
What if the level was 4?
Discharge Advice
Yearly influenza vaccine
Has she had Pneumovax (due at 2 yo)?
PCN VK 125 mg PO BID
Folate 1 mg PO daily
Follow up in your office
Case 3
Tony is a 16 yo AAM with HbSS disease
who comes into the ER with a cough for
24 hours and pain in his left chest.
He denies fever at home, denies SOB,
denies priapism. He is on hydroxyurea at
home. He has received multiple
transfusions.
What next?
Physical exam
Are there crackles? Is he tachypneic? Is
he febrile? What is his O2 sat?
CXR: left lower lobe infiltrate
What next?
Medications? He weighs 70 kg and has
no allergies
Other therapies?