CLINICAL PATHWAY

PEDIATRIC ACUTE CHEST SYNDROME (ACS)

Algorithm- Acute Chest Syndrome Management

Sickle Cell Pain Guideline

Apheresis Catheter Guidelines: Short Term Use
Automated Red Blood Cell Exchange for Sickle Cell Patients (CHCO DSR)

Page 1 of 11
CLINICAL PATHWAY

TABLE OF CONTENTS
Algorithm
Target Population
Background | Definitions
Initial Evaluation-N/A
Clinical Management
Diagnostic Tests
Fluids | Nutrition
Respiratory Therapy
Table 1. Clinical Respiratory Score (CRS)
Treatment
Table 2. Antimicrobial Medication
Table 3. Pain Medication
Table 4. Respiratory Medication
Discharge Criteria
Related Children’s Hospital Colorado Documents
References
Clinical Improvement Team

TARGET POPULATION

Inclusion Criteria
• Patients with sickle cell disease (SS, SC, Sβ0 thalassemia, Sβ+ thalassemia, other sickle cell disease variants)

Exclusion Criteria
• Patients without infiltrate on chest radiograph (e.g., asthma exacerbation)
• Patients with previously known severe pulmonary hypertension
o Tricuspid Regurgitant Velocity (TRV) >=3 m/s or confirmation by right heart catheterization
• Patients post bone marrow transplant

BACKGROUND | DEFINITIONS
Acute chest syndrome (ACS) is the second most common reason for hospitalization in children with sickle cell disease
and a leading cause of mortality. ACS is defined as a new pulmonary infiltrate on chest radiograph with evidence of
lower respiratory tract disease (e.g., some combination of cough, shortness of breath, retractions, rales, hypoxia, chest
pain etc.) with or without fever. In the majority of cases of ACS, a source is not identified. The most commonly
identified etiology of ACS is infection, but it may also result from pulmonary vaso-occlusion, pulmonary infarction, fat
embolism or hypoventilation. The primary infectious agents implicated in ACS include Chlamydia pneumoniae,
Mycoplasma pneumoniae, Streptococcus pneumoniae, and viruses. Risk factors for ACS include vaso-occlusive pain
crisis, anesthesia, and surgery. Patients are at increased risk for stroke in the two weeks immediately following an
episode of ACS.

Page 2 of 11
CLINICAL PATHWAY

CLINICAL MANAGEMENT
• Admit to hematology service at Anschutz or Colorado Springs campuses
• Vital signs q 2-4 hours depending upon degree of respiratory compromise
• Record pain score every 4 hours
• Continuous cardiorespiratory monitor and pulse oximetry
• Maintain oxygen saturations ≥95% in order to prevent additional red cell sickling. Frequent assessments of
respiratory status. May refer to the clinical respiratory score (CRS) Table 1 for a means of objective monitoring.
• Encourage ambulation: out of bed to chair or ambulating at least 2-3 times per day
• Appropriate isolation precautions
• Continue medication for reactive airway disease if applicable. Steroids should be used with caution as their use
may be associated with increased “rebound” acute pain episodes and rehospitalization.
• Encourage incentive spirometry use. May use pinwheels in younger patients. Some patients may benefit from
EZPap.
• Consider simple transfusion after discussion with hematology attending to achieve a hemoglobin of 10 g/dL to
decrease the percentage of circulating sickle cells. For patients who are at 10 or higher, an automated red blood
cell exchange (RBE) should be strongly considered (see treatment section for additional details)

DIAGNOSTIC TESTS
• CBC with differential, CMP, platelet count, and reticulocyte count initially and daily until improving (compare with
patient's baseline values)
• Order an initial type & screen and then prn
• CXR initially, repeat for respiratory decompensation (be aware that the x-ray often underestimates the degree of
involvement and may appear worse when the child is clinically improving)
• Blood cultures (do not need to repeat daily)
• Viral testing as appropriate
• Consider:
o If severe abdominal pain, consider an ultrasound for gallstones
o Echocardiography is not recommended routinely in patients with acute chest syndrome. Consult cardiology
if concern for pulmonary hypertension arises (prolonged hypoxemia, fixed split S2 or pronounced pulmonary
component of S2, hepatomegaly, persistent peripheral edema, or persistent pulmonary edema despite
adequate fluid status)

FLUIDS | NUTRITION
• Daily weight
• Record intake and output strictly
• Maintain "euvolemia". Encourage oral hydration. If IV fluids are needed use IV + P.O. = 1 x maintenance order.
More fluid is appropriate only if patient is dehydrated or if insensible losses are increased (e.g., persistent fever),
but boluses are preferred over increased fluid rates. IV fluid should be D5 1/4 NS to avoid exacerbating the
sickling process.

Page 3 of 11
CLINICAL PATHWAY

RESPIRATORY THERAPY
• Consult Pulmonology
• Maintain oxygen saturations ≥95%
• Clinical features suggestive of asthma or acute bronchospasms; trial Albuterol 4 puffs with a spacer or 2.5 mg
nebulized once. Reassess patient. If improvement is noted, order Albuterol 2-4 puffs or Albuterol 2.5mg
nebulized Q4 and PRN. If at any time CRS worsens by 2 or more may increase frequency of the Albuterol and
notify the provider
• Steroids should be used cautiously as they have been associated with rebound pain crises and readmissions.
• Consider lung expansion strategies to include EZPAP and/or IS to support bronchial hygiene: EzPAP (along with
IS) Q4 hours for 72 hours. 72 hours after the initiation of the therapy, the patient will be evaluated by the
respiratory therapist for pulmonary stability. If the chest x-ray (if done) remains stable, there are no signs of
pulmonary infection, there is good aeration throughout all lung fields upon auscultation, and the patient can
consistently achieve 14mL/kg with the IS, the EzPAP will then be discontinued. The patient will then receive IS
Q2 hours while awake and Q4 hours at night by their RN
• Transfer to the ICU if patient is requiring escalating respiratory support, or if invasive or non-inavsive (CPAP,
BiPAP) mechanical ventilation is being considered

TABLE 1. CLINICAL RESPIRATORY SCORE (CRS)

ASSESS SCORE 0 SCORE 1 SCORE 2

RR 1-5 YEARS: <30; >5 1-5 YEARS: 30-40; >5 1-5 YEARS: >40; >5
YEARS: <20 YEARS: 20-30 YEARS: >30

AUSCULTATION GOOD AIR MOVEMENT, DEPRESSED AIR DIMINISHED OR ABSENT

SCATTERED WHEEZING MOVEMENT, BREATH SOUNDS,
(ONLY EXPIRATORY), INSPIRATORY AND SEVERE WHEEZING, OR
LOOSE CRACKLES EXPIRATORY WHEEZES MARKED PROLONGED
EXPIRATION

USE OF MILD TO NO USE OF MODERATE SEVERE INTERCOSTAL

ACCESSORY ACCESSORY MUSCLES. INTERCOSTAL AND SUBSTERNAL
MUSCLES MILD TO NO RETRACTIONS, MILD TO RETRACTIONS, NASAL
RETRACTIONS OR MODERATE USE OF FLARING
NASAL FLARING ON ACCESSORY MUSCLES,
INSPIRATION NASAL FLARING

MENTAL NORMAL TO MILDLY IRRITABLE, AGITATED, LETHARGIC

STATUS IRRITABLE RESTLESS

ROOM AIR SPO2 >95% 90-95% <90%

COLOR NORMAL PALE TO NORMAL CYANOTIC, DUSKY

Page 4 of 11
CLINICAL PATHWAY

TREATMENT
Antipyretics
• Acetaminophen dose according to CHCO Formulary PRN temperature greater than or equal to 38.3oC after
blood cultures have been obtained on at least one occasion

Antibiotics (see Table 2 for choices and doses)

Ampicillin and azithromycin are the regimen of choice for initial inpatient management
o If there is a known or suspected penicillin allergy (excluding a SCAR, see details below), ceftriaxone
should be used as second line therapy.
o If cephalosporine allergy, levofloxacin is the regimen of choice and azithromycin can be omitted
because levofloxacin has adequate coverage of atypical organisms
o Strongly consider adding vancomycin for severe illness, or if large infiltrate with pleural effusion
present and S. aureus is suspected
o Consider discontinuing azithromycin if respiratory viral panel is negative for M. pneumoniae and C.
pneumoniae
Hold home penicillin prophylaxis if receiving broad-spectrum antibiotics
o If antibiotics are continued upon discharge, an appropriate oral antibiotic should be continued to
complete a course of 5 days (including inpatient IV therapy received): Amoxicillin is recommended as
first line, cefpodoxime is the drug of choice in the presence of a penicillin allergy, and levofloxacin is
the drug of choice in the presence of a cephalosporin allergy. Patients may be candidates for penicillin
delabeling through the Penicillin Allergy Delabeling Clinical Pathway and then receive ampicillin (first
line therapy).
o If the allergy history with PCN is consistent with a severe cutaneous adverse drug reaction (SCAR)
(i.e., SJS/TEN, DRESS etc.), consider consulting allergy & immunology prior to administration of
ceftriaxone. While these are exceedingly rare, the cross reactivity between penicillin's and
cephalosporins is not well characterized in these conditions. The Penicillin Allergy Delabeling Clinical
Pathway also has questions to evaluate for SCARs

Analgesia (if indicated)

• If pain is present patients should start on scheduled anti-inflammatories and opiates if there are no
contraindications
o Start ketorolac, but limit to 48-hour maximum duration then start ibuprofen PO q6h (not PRN) if no
contraindication present (i.e., gastritis, ulcer, coagulopathy, renal impairment).
o If pain does not respond to anti-inflammatory alone, consult the sickle cell vaso-occlusion guidelines.
Be aware narcotic administration may further suppress respiration

Transfusions
• Consider giving a simple blood transfusion (discuss volume with Hematology) to achieve a hemoglobin of 10
g/dL. This effectively reduces the % sickle cells. If baseline hemoglobin is near or above 10 g/dL, and
symptomatic, strongly consider automated red cell exchange procedure. Do not transfuse acutely to
hemoglobin greater than 10 g/dL, hematocrit greater than 30 percent if percent sickle hemoglobin is or is
presumed to be greater than 30 percent since it is associated with inducing pain and stroke
o Blood orders should include the following specifications:
 No irradiation (unless receiving myeloablative chemotherapy as part of preparative regiment
for bone marrow transplantation)
 Phenotypically matched (which will trigger the hemoglobinopathy blood bank protocol)

Page 5 of 11
CLINICAL PATHWAY

Automated Red Blood Cell Exchange (RCE)

• Indications:
o Severe respiratory distress (CRS ≥4)
o Persistent increase in O2 requirement or rapid decompensation
o Worsening of clinical exam (not attributable to fluid overload)
o If transfusion needed and Hgb at 10 g/dL or greater
o PICU admission or transfer
o NIPPV or intubation
• Automated RCE Process
o If patient is located in Colorado Springs or a network of care site, they should be sent to the Anschutz
campus as apheresis services are not available elsewhere.
o Place Apheresis Consultation through EPIC and contact on-call TM provider.
o Appropriate central line placement is often the time-limiting factor. Central venous catheter placement
is usually required. See Apheresis Catheter Guidelines: Short Term Use for appropriate size catheter
options
 Options include:
• Power PICC line placement (consultation with Interventional Radiology)
• In emergent situations, line placement by the ICU may be more appropriate (i.e.,
double lumen femoral or IJ catheter).
• Remove central venous catheters as soon as possible after exchange procedure(s) to reduce the risk for
thrombosis.
o Red blood cell exchange hematologic targets are a HgS percentage <30% and end procedure
hematocrit of 30%.
o Pre- and post-exchange hemoglobin variant samples will be ordered by the TM provider.

TABLE 2. ANTIMICROBIAL MEDICATIONS

Medication Dosing Indication/Notes
Antimicrobial – Outpatient 1st Choice
90 mg/kg/day (maximum 3,000 mg/day) PO divided
Amoxicillin (PO) TID x 5 days Discontinue prophylactic penicillin while
patient is receiving amoxicillin.
200 mg/kg/day (maximum 8,000 mg/day) IV divided
Ampicillin (IV) every 6 hours Antimicrobial – Inpatient 1st Choice

Antimicrobial – Inpatient/Atypical
Coverage

10 mg/kg/day (maximum 500 mg/day) PO x 1 dose, Discontinue if RPP results negative for
Azithromycin (IV/PO)
followed by 5 mg/kg/day (maximum 250 mg/day) PO Chlamydophila and Mycoplasma
*Highly Bioavailable* once daily x 4 doses
Not necessary to use azithromycin with
levofloxacin as levofloxacin covers
atypical bacteria
Antimicrobial – Outpatient for penicillin
10 mg/kg/day (maximum 400 mg/day) PO divided
Cefpodoxime (PO) BID
allergy

Page 6 of 11
CLINICAL PATHWAY

*Ensure prescription sent in advance

(variable stock at some outpatient
pharmacies)
May consider cefuroxime or cefprozil if
unable to obtain cefpodoxime
Antimicrobial – Outpatient clinic or
emergency department ; transition to
ampicillin upon admission for ACS
Ceftriaxone (IV) 50 mg/kg/day (maximum 2,000 mg/day) IV q24h
Discontinue prophylactic penicillin while
patient is receiving broad-spectrum
antimicrobials
Antimicrobial – Inpatient and/or
Less than 5 years: Levofloxacin 20 mg/kg/day Outpatient for cephalosporin allergy
(maximum 500 mg/day) IV or PO divided q12h
Discontinue prophylactic penicillin while
Levofloxacin (IV/PO) 5-10 years: 14 mg/kg/day (maximum 500 mg/day) IV patient is receiving broad-spectrum
*Highly Bioavailable* or PO divided q12h antimicrobials

Not necessary to use azithromycin with

Greater than 10 years: 10 mg/kg/day (maximum 500 levofloxacin as levofloxacin covers
mg/day) IV or PO q24h atypical bacteria
Antimicrobial – Inpatient for patients
with
severe illness or with large infiltrate with
Contact pharmacy for recommended dosing pleural effusion present and S. aureus
Vancomycin (IV) suspected
Dosing interval based on age/renal function
*Must monitor renal function (SCr, BUN,
urine output) at baseline and minimum
twice weekly thereafter

TABLE 3. RESPIRATORY MEDICATION TABLE

Medication Dosing Indication/Notes
4 puffs MDI OR 2.5 mg nebulized x 1 dose. If
Increased work of breathing
effective (improved working of breathing, respiratory
Albuterol rate, wheezing, aeration) order scheduled albuterol
MDI 2-4 puffs with spacer or 2.5mg nebulized q4h
1 mg/kg (maximum 40 mg/dose) PO/IV q12h x 5
days
Followed by steroid wean to prevent rebound:
0.5 mg/kg (maximum 20mg/dose) PO/IV q12h x 3
Consider in patients if
days
wheezing/crackles/rales present or
Prednisone or 0.5 mg/kg (maximum 20mg/dose) PO/IV q24h x 3
history of concurrent asthma
Methylprednisolone days
exacerbation
0.25 mg/kg (maximum 20mg/dose) PO/IV q24h x 3
days
*Use of steroids has been associated with rebound
pain crisis and readmissions; hold until further
discussed with heme
PO: Less than 3 months- 0.5mg/kg/dose once daily
greater than or equal to 3 months- 0.5mg/kg/dose,
(max dose 20mg) BID.
Famotidine IV: less than 3 months - 0.25mg/kg/dose once daily
GI prophylaxis for steroid use
greater than or equal to 3 months- 0.25mg/kg/dose
(max dose 20mg) BID
Consider if signs of fluid overload
Furosemide 0.5 – 1 mg/kg (maximum 40 mg/dose)
present

Page 7 of 11
CLINICAL PATHWAY

TABLE 4. PAIN MEDICATION

Medication Dosing Indication/Notes
Temperature greater than or equal to
Dose according to manufacturer’s recommendations
Acetaminophen Maximum daily dose 75 mg/kg/day or 4,000 mg/day
38.3°C

Ketorolac 0.5 mg/kg (maximum 30 mg/dose) IV q6h x 48 hours Pain/inflammation

10 mg/kg (maximum 600 mg/dose) PO q6 after 48-
Ibuprofen hours of ketorolac completed Pain/Inflammation
Maximum daily dose 2,400 mg/day
0.1 – 0.15 mg/kg (maximum 8 mg/dose) IV x 1 dose
followed by 0.05 – 0.15 mg/kg (maximum 4
mg/dose) IV q2-4hr Pain
PCA Dosing:
Morphine PCA Dose: 0.01 – 0.02 mg/kg (maximum 10 mg/hr) *Obesity defined as greater than 95th
with lockout of 8 minutes percentile BMI for age in children > 2
Continuous Rate: 0.03 – 0.05 mg/kg/hr years old
* Morphine should be dosed on IBW in obese
patients
Intermittent Dosing:
0.015 – 0.02 mg/kg (maximum 2 mg/dose) followed
by 0.015 – 0.02 mg/kg (maximum 1 mg/dose) q3-4hr Pain
PCA Dosing:
Hydromorphone PCA Dose: 2-3 mCg/kg (maximum dose 1.2 mg/hr) *Obesity defined as greater than 95th
with lockout of 8 minutes percentile BMI for age in children > 2
Continuous Rate: 3 – 5 mCg/kg/hr years old
*Hydromorphone should be dosed on adjusted BW
in obese patients

DISCHARGE CRITERIA
• Afebrile >24 hours
• Improved pulmonary symptoms and documentation of adequate oxygenation on room air. Home oxygen may be
appropriate to maintain baseline oxygen saturations for a short time as an outpatient.
• Negative cultures for greater than or equal to 24-48 hours
• Stable hemoglobin/hematocrit for at least 24 hours
• Taking adequate oral fluids and able to take oral medications if applicable
• Adequate pain relief, if needed, with oral analgesics
• Follow-up plans coordinated with sickle cell team. Patients discharged with oxygen should return to clinic in 1
week. All patients require a follow up CXR 4-6 weeks from discharge
• Pulmonology follow up arranged

RELATED CHILDREN’S HOSPITAL COLORADO DOCUMENTS

• Apheresis Catheter Guidelines: Short Term Use

• Bronchial Hygiene Therapy Policy

Page 8 of 11
CLINICAL PATHWAY

REFERENCES
1. Vichinsky E et al. Causes and outcomes of the acute chest syndrome in sickle cell disease. National Acute Chest
Syndrome Study Group. NEJM 2000. 342: 1855-1865.
2. Yawn B et al. Management of sickle cell disease: Summary of the 2014 evidence-based report by expert panel
members. JAMA 2014. 312: 1033-1048.
3. Howard J et al. Guidelines on the management of acute chest syndrome in sickle cell disease. BJH 2015. 169:
492-505.
4. Sobota A et al. Corticosteroids for acute chest syndrome in children with sickle cell disease: Variation in use and
association with length of stay and readmission. Am J Hemat 2010; 85(1): 24-28.
5. Ahmad F et al. The use of incentive spirometry in pediatric patients with sickle cell disease to reduce the incidence
of acute chest syndrome. J Pedatr Hematol Oncol 2011. 33: 415-420.
6. Bellet PS, Kalinyak KA, Shukla R et al. Incentive spirometry to prevent acute pulmonary complications in sickle cell
diseases. NEJM 1995; 333(11): 699-703.
7. Saylors R et al. Comparison of automated red cell exchange transfusion and simple transfusion for the treatment
of children with sickle cell disease acute chest syndrome. Pedatr Blood Cancer 2013. 60: 1952-1956.
8. Reagan M et al. Multi-modal intervention for the inpatient management of sickle cell pain significantly decreases
the rate of acute chest syndrome. Pediatr Blood Cancer 2011; 56:262-266.
9. Saylors R et al. Comparison of automated red cell exchange transfusion and simple transfusion for the treatment
of children with sickle cell disease acute chest syndrome. Pediatr Blood Cancer 2013; 60: 1952-1956.
10. Turner J et al. Exchange versus simple transfusion for acute chest syndrome in sickle cell anemia adults.
Transfusion 2009; 49: 863-868.
11. Velasquez M et al. Erythrocytapheresis in children with sickle cell disease and acute chest syndrome. Pediatr
Blood Cancer 2009; 53: 1060-1063.
12. Stella T. Chou, Mouaz Alsawas, Ross M. Fasano, Joshua J. Field, Jeanne E. Hendrickson, Jo Howard, Michelle
Kameka, Janet L. Kwiatkowski, France Pirenne, Patricia A. Shi, Sean R. Stowell, Swee Lay Thein, Connie M.
Westhoff, Trisha E. Wong, Elie A. Akl; American Society of Hematology 2020 guidelines for sickle cell disease:
transfusion support. Blood Adv 2020; 4 (2): 327–355.

Page 9 of 11
CLINICAL PATHWAY

CLINICAL IMPROVEMENT TEAM MEMBERS

Chris McKinney, MD | Hematology
Ashley Sabus PharmD, BCOP | Pharmacy
Chris Ruzas, MD | PICU
Michele Loi, MD | PICU
Erin Barthelmess, PharmD, BCOP | Pharmacy
Irina Topoz, MD | Emergency Medicine
Joan MacKenzie MS, APRN, CPNP-PC CPEN | CPS, Emergency Medicine
Karol Kerr, MD | Oncology
Grace Houser, MD | Pulmonary
Melissa Chaput, RT | Respiratory Therapy
David Nash | Pharmacy
Patrick Cripe, MD | PICU
Kashina Meyers | Clinical Social Work
Leanne Adamson | CNS CCBD

APPROVED BY
Clinical Care Guideline and Measures Review Committee – October 25, 2022
Antimicrobial Stewardship Committee – January 3, 2023
Pharmacy & Therapeutics Committee – September 1, 2022

Clinical Care Guidelines/Quality

MANUAL/DEPARTMENT
November 24, 2015
ORIGINATION DATE

LAST DATE OF REVIEW OR REVISION October 25, 2022

Michael DiStefano, MD
COLORADO SPRINGS REVIEWED BY
Chief Medical Officer, Colorado Springs

Lalit Bajaj, MD, MPH

APPROVED BY Chief Quality and Outcomes Officer, Clinical Effectiveness

REVIEW/REVISION SCHEDULE
Scheduled for full review on October 25, 2026

Page 10 of 11
 CLINICAL PATHWAY

Clinical pathways are intended for informational purposes only. They are current at the date of publication and are reviewed on a
regular basis to align with the best available evidence. Some information and links may not be available to external viewers.
External viewers are encouraged to consult other available sources if needed to confirm and supplement the content presented in
the clinical pathways. Clinical pathways are not intended to take the place of a physician’s or other health care provider’s advice,
and is not intended to diagnose, treat, cure or prevent any disease or other medical condition. The information should not be used
in place of a visit, call, consultation or advice of a physician or other health care provider. Furthermore, the information is provided
for use solely at your own risk. CHCO accepts no liability for the content, or for the consequences of any actions taken on the basis
of the information provided. The information provided to you and the actions taken thereof are provided on an “as is” basis without
any warranty of any kind, express or implied, from CHCO. CHCO declares no affiliation, sponsorship, nor any partnerships with any
listed organization, or its respective directors, officers, employees, agents, contractors, affiliates, and representatives.

Clinical pathways are intended for informational purposes only. They are current at the date of publication and are reviewed on a
regular basis to align with the best available evidence. Some information and links may not be available to external viewers.
External viewers are encouraged to consult other available sources if needed to confirm and supplement the content presented in
the clinical pathways. Clinical pathways are not intended to take the place of a physician’s or other health care provider’s advice,
and is not intended to diagnose, treat, cure or prevent any disease or other medical condition. The information should not be used
in place of a visit, call, consultation or advice of a physician or other health care provider. Furthermore, the information is provided
for use solely at your own risk. CHCO accepts no liability for the content, or for the consequences of any actions taken on the basis
of the information provided. The information provided to you and the actions taken thereof are provided on an “as is” basis without
any warranty of any kind, express or implied, from CHCO. CHCO declares no affiliation, sponsorship, nor any partnerships with any
listed organization, or its respective directors, officers, employees, agents, contractors, affiliates, and representatives.

Page 11 of 11