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 scaleIs 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 packsPT consult for ROM, TENS unit, whirlpoolEncourage 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 differentialReticulocyte countCRPBlood cultureChest X-ray

Labs that you might want

CP14UA, urine cultureParvovirus 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 icterusT=99, HR=80, RR=16, BP 110/70, O2 sats

97% RA1/6 SEMLeg without erythema or wounds, mild

TTP, CR brisk

Labs

H/H 10/30Retic 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 hospitalLabs?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 vaccineHas she had Pneumovax (due at 2 yo)?PCN VK 125 mg PO BIDFolate 1 mg PO dailyFollow 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 examAre 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?