TEXAS CHILDREN'S HOSPITAL
EVIDENCE-BASED CLINICAL DECISION SUPPORT
DATE 1/2008
ACUTE CHEST SYNDROME (ACS) GUIDELINE
Definition: Acute illness associated with lower respiratory
symptoms, new hypoxemia, or new infiltrate on Chest Xray. It is a leading cause of hospitalization and death in
(1,2)
children [and adults] with sickle cell disease.
It is
(3)
estimated to account for 25% of SCD related deaths.
Pathophysiology: About half of the patients diagnosed
with ACS develop the respiratory complication during
hospitalization for another diagnosis such as pain crisis.
Opioid analgesics, post-operative atelectasis, and asthma
(1)
may promote the development of an ACS episode.
Although the etiology is undetermined in many cases,
pulmonary infarction, fat embolism, and infection are now
recognized as important causes of ACS. Chlamydia
pneumoniae, Mycoplasma pneumoniae, Streptococcous
pneumoniae, Staphylococcus aureus and parvovirus are
(2)
some of the pathogens commonly isolated.
Diagnosis: Clinical history, physical examination and
chest X-Ray are used to diagnose ACS.
History: Assess for
 Lower respiratory symptoms (cough, wheezing,
tachypnea, chest pain)
 Fever
 Previous history of ACS episode
Physical Examination
 Assess respiratory rate (RR), use of accessory
muscles, color.
 Auscultate lungs
 Obtain pulse ox. Detect new onset hypoxemia
 Rate severity of ACS according to Clinical Respiratory
Score
Table 1. ACS Clinical Respiratory Score (21)
Assess
A
RR
B
Auscultation
C
Use of
Accessory
Muscles
D
Mental
Status
E
Room Air
SpO2
Color
F
Score 0
Score 1
Score 2
1-5 years <30
> 5 years <20
Good air
movement,
expiratory
scattered
wheezing or
loose
rales/crackles
1-5 years 30-40
> 5 years 20-30
Depressed air
movement,
inspiratory and
expiratory
wheezes or
rales/crackles
Mild to no
use of
accessory
muscles.
Mild to no
retractions or
nasal flaring
on inspiration.
Normal to
mildly
irritable
> 95%
Moderate
intercostals
retractions, mild
to moderate use
of accessory
muscles, nasal
flaring.
1-5 years >40
> 5 years >30
Diminished or
absent breath
sounds,
severe
wheezing or
rales/crackles
or marked
prolonged
expiration.
Severe
intercostals
and substernal
retractions,
nasal flaring
Normal
Irritable,
agitated, restless
Lethargic
90-95%
<90%
Pale to normal
Cyanotic,
dusky
Add score from A to F to obtain the total CRS score.
(see Table 1)
Guideline Eligibility Criteria
Age 1-21 years
Patient with Sickle Cell Disease
Principles of Clinical Management
(see Table 2)
Guideline Exclusion Criteria
Patients without sickle cell disease
Critical Points of Evidence
Evidence Supports
Use of incentive spirometry in patients with vaso-occlusive
(13,22)
crisis (VOC) decreases development of ACS
Evidence Lacking/Inconclusive
Use of IV steroids for pain crisis (rapid recovery vs
(5,6,12)
rebound effect)
Early use of Packed Red Blood Cells (PRBC) in patients
(5,23)
with vaso-occlusive crisis (VOC) can prevent ACS
Serum phospholipase A2 (sPLA2) could be used as a
(23)
screening tool
1
Table 2. Principles of Clinical Management
RECOMMEND

MONITORING






DIAGNOSTICS

Vital signs (blood pressure, heart rate, respiratory rate)
every 4 hours
Pulse oximetry every 12 hours or continuous
(encouraging ambulation)
Weigh daily
Strict charting of fluid intake / output
Pain severity rating minimum every 4 hours
Monitor Clinical Respiratory Scale (CRS) at least
every 4 hours (see table1) if CRS 2 follow ACS
Respiratory Support management flowchart
CBC, differential, platelet count and reticulocyte count
(initially & daily until improving—compare with patient´s
baseline values)
CXR if cough, chest pain, hypoxemia or any respiratory
symptoms present or develop after admission
CONSIDER




FLUIDS,
NUTRITION,
GENERAL CARE

Total fluid intake [intravenous plus oral] at 1x
maintenance.

Encourage ambulation, activity

IF patient  5 yo use Incentive Spirometry (IS) as follows:


Supervised Incentive spirometry [IS] - 10 breaths every 2
hours between 8 AM and 10 PM. Alternate the use of positive
expiratory pressure (PEP).
IS should be documented alternately by respiratory therapist
and nursing services.
OXYGEN
PAIN
MANAGEMENT
ANTIBIOTICS
Maintain pulse ox > 94%
Notify care providers of increased FiO2 requirement or
increase in CRS score
Acetaminophen Per Protocol PRN T>100.4F
(MAX: 75 mg/kg/day, not to exceed 4,000 mg/day)
Morphine 0.1-0.2 mg/kg/dose IV every 2 hours OR PRN pain
OR PCA (MAX: 15mg/dose)
Ibuprofen: (if no contraindications) 10 mg/kg/dose PO every
6-8 hours (MAX: 800 mg/dose, not to exceed 40mg/kg/day or
2,400 mg/day) – Limit frequent dosing to 72 hour duration
Ketorolac (if no contraindications, administer either ketorolac
OR ibuprofen) 0.5 mg/kg/dose IV every 6 hours for 5 days
(MAX: 30 mg/dose) – Do not exceed 5 days/month

Discontinue prophylactic penicillin while on wide
spectrum antibiotics



IF history of recent fever CONSIDER Blood
culture
IF severe illness or Hb >1g/dL below baseline Hb
strongly CONSIDER Type & crossmatch
IF severe illness CONSIDER BUN, creatinine,
ALT, AST, bilirubin,
IF severe abdominal pain CONSIDER abdominal
ultrasound
IF patient is dehydrated or insensible losses are
increased as with persistent fever ADMINISTER
more fluids.
IF patient < 5 yo:
CONSIDER introducing the use or IS and PEP
depending on cooperation.
CONSIDER making the patient blow soap
bubbles
IF febrile, Cefuroxime 50 mg/kg/dose IV every 8
hours (MAX: 1,500 mg/dose)
IF patient is PENICILLIN/CEPHALOSPORIN
ALLERGIC, Substitute Clindamycin
10 mg/kg/dose IV every 6-8 hours (MAX: 900
mg/dose)
IF severe illness CONSIDER addition of
Vancomycin; for children <70 kg: 15 mg/kg/dose
IV every 8 hours; for children ≥70 kg: 1,000 mg IV
every 12 hours (MAX: 1,000 mg/dose)
2
ACS RESPIRATORY SUPPORT MANAGEMENT
Patient meets ACS criteria
Acute illness associated with lower respiratory symptoms, new hypoxemia, or new infiltrate on Chest X-ray







FOLLOW Flowchart for SCD patients with pain and fever with the following modifications:
Encourage ambulation (may come off pulse oximeter to ambulate)
ADD Azithromycin: 10 mg/kg PO on day 1 [MAX: 500 mg/dose], then 5 mg /kg PO once daily [MAX: 250 mg/dose] for 4 days. (Erythromycin may be
substituted)
CXR initially, repeat for clinical deterioration
Continue Incentive spirometry in patients  5years as follows: 10 breaths IS and 10 breaths PEP alternating every 2 hours between 8 AM and 10 PM
In patients < 5 years old, PEP and/or IS can be introduced, but lack of cooperation should lead to earlier consideration of use of vest therapy.
CONSIDER adding Vancomycin
CONSIDER Furosemide 0.5 mg/kg IV x 1dose. IF signs of fluid overload (MAX: 40 mg/dose)
Assess patient according to Clinical Respiratory Scale
CRS 2-3


Vital signs every 4 hours
Contiuous pulse oximeter. Goal SpO2 ≥
94%

Transfuse to Hb goal of 9-10 g/dL

Continue IS + PEP every 2 hours
IF Patient < 5 years

Vest TID if  10kg
IF Patient not wheezing: ≥ 5 years

Vest or IPV TID (vest preferred)
IF Wheezing or rales/crackles present

Vest TID

Inhaled bronchodilator per beta2
agonist protocol

Methylprednisolone 1mg/kg/dose IV
every 12 hours (MAX: 80mg/day)

Ranitidine for GI prophylaxis

Measure Peak Expiratory Flow (PEF)
BID
CRS 4


Vital signs every 2 hours
Continuous pulse oximeter. Goal
SpO2 ≥ 94%

Transfuse to Hb goal of 9-10
g/dL

Transfer to PCU

IPV or Vest therapy to every 4
hours .

Inhaled bronchodilator per
beta2 agonist protocol

Consider BiPAP
IF Wheezing or rales/crackles
present

Vest every 4 hours

Methylprednisolone
1mg/kg/dose IV every 6 hours
(MAX: 80mg/day)

Ranitidine for GI prophylaxis

Measure PEF BID
CRS ≥6
CRS 5


Vital signs every 2 hours
Continuous pulse oximeter. Goal SpO2 ≥
94%

Transfuse to Hb goal of 9-10 g/dL.
Consider exchange transfusion to 10 g/dl
and Hb S  25% or Hb S+C  25%

Transfer to PCU or PICU. Consider
management in PICU if history of
previous ACS episode with exchange
transfusion.

CCM consult upon admission and
Pulmonary Service Consult at least prior
to discharge

BiPAP + IPV every 4 hours

Inhaled bronchodilator per beta2 agonist
protocol
IF Wheezing or rales/crackles present

Vest every 4 hours

Methylprednisolone 1mg/kg/dose IV
every 6 hours (MAX: 80mg/day)

Ranitidine for GI prophylaxis

Measure PEF BID


Vital signs every 2 hours
Continuous pulse oximeter.
Goal SpO2 ≥ 94%

Perform exchange transfusion
Remove Venous Catheters as
soon as possible after
exchange transfusion

Manage in PICU

BiPAP + IPV

Inhaled bronchodilator per
beta2 agonist protocol
IF Wheezing or rales/crackles
present

Vest every 4 hours

Methylprednisolone
1mg/kg/dose IV every 6 hours
(MAX: 80mg/day)

Ranitidine for GI prophylaxis

Measure PEF BID
3
Discharge Criteria (1)
 Improved pulmonary symptoms and documentation of adequate oxygenation on room air
 Afebrile 24h and negative cultures for  24-48 h if applicable
 Stable hemoglobin/hematocrit.
 Taking adequate oral fluids and able to take PO medications if applicable
 Adequate pain relief, if needed, with oral analgesics
 Slow wean from steroids (over 7-10 days)
Parent understands
 discharge care, including steroid wean
 when Hematology Clinic and Pulmonary SCD Clinic follow-ups scheduled
Home care agencies notified as needed
Follow-Up


Follow-up plans coordinated with hematology service to consider disease modifying therapy
(Hydroxyurea, chronic transfusions,stem cell transplantation)
Follow up in Pulmonary Sickle Cell Clinic if CRS  3 any time during hospital admission,
should have formal Pulmonary Function Tests performed on the same day
4
References
1. Lane P, Buchanan G, Hutter J, Austin R, Britton H, Rogers Z, et al. Sickle cell disease in children
and adolescents: Diagnosis, guidelines for comprehensive care, and care paths and protocols
for management of acute and chronic complications. 2001
2. Vichinsky E, Neumayr L, Earles A, Williams R, Lennette E, Dean D, et al. Causes and outcomes of
the acute chest syndrome in sickle cell disease. NEJM. 2000; 342: 1855-65
3. Castro O, Brambilla D, Thorington B, Reindorf C, Scott R et al. The Acute Chest Syndrome in Sickle
Cell Disease: Incidence and Risk Factors. Blood 1994; 2: 643-648
4. Ohene-Frempong, Weiner S, Sleeper L, Miller S, Embury S, Moohr J et al. Cerebrovascular Accidents
in Sickle Cell Disease: Rates and Risk Factors. Blood 1998; 91:288-294
5. Ballas S. Sickle Cell Anaemia: Progress in Pathogenesis and Treatment. Drugs 2002; 62(8):11431172
6. Knight J, Murphy T and Browning I. The Lung in Sickle Cell Disease. Pediatric Pulmonology.1999.
28:205-216.
7. Dreyer Z. Chest Infections and Syndromes in Sickle Cell Disease of Childhood. Seminars in
Respiratory Infections.1996; 11(3):163-172
8. Stuart M and Setty Y. Acute chest syndrome of sickle cell disease:new light on an old problem.
Curr Opin in Hematol.2001:111-120
9. Needleman J,Benjamin L,Sykes J and Aldrich T. Breathing patterns during vaso-occlusive crisis of
sickle cell disease. Chest.2002; 122(1):43-46
10. Swerdlow P. Red Cell Exchange in Sickle Cell Disease. Hematology 2006
11. Lawson S,, Oakley S, Smith N, Bareford D. Red cell exchange in sickle cell disease. Clin Lab Haem
1999; 21:99-102.
12. Bernini JC, Rogers Z, Sandler E, Reisch J, Quinn C, Buchanan G. Beneficial effect of intravenous
dexamethasone in children with mild to moderately severe acute chest syndrome complicating
sickle cell disease. Blood 1998; 92: 3082-89
13. Bellet P, Kalinyak K, Shukla R, Gelfand M and Rucknagel D. Incentive spirometry to prevent acute
pulmonary complications in sickle cell diseases. NEJM. 1995; 333:699-703
14. Kress JP,Pohlman AS, Hall JB. Determination of Hemoglobin Saturation in Patients with Acute
Sickle Chest Syndrome: A comparison of arterial blood gases and pulse oximetry. Chest 1999;
115:1316-1320.
15. Needleman JP, Setty BN, Valotta L, Dampler C and Allen J. Measurement of Hemoglobin Saturation
by Oxygen in children and Adolescents With Sickle Cell Disease. Pediatric Pulmonology 1999; 28:
423-428.
16. Langenderfer B. Alternatives to percussion and postural drainage: A review of mucus clearance
therapies: Percussion and postural drainage, autogenic drainage, positive expiratory pressure,
flutter valve, intrapulmonary percussive ventilation, and high frequency chest compression with
the ThAIRapy vest. Journal Of Cardiopulmonary Rehabilitation. 1998; 18:283-289.
17. McCool FD, Rosen MJ. Nonpharmacologic Airway Clearance Therapies: ACCP Evidence-Based
Clinical Practice Guidelines. Chest. 2006; 129:250-259.
18. Elkins MR, Jones A, Van der Schans C. Positive expiratory pressure physiotherapy for airway
clearance in people with cystic fibrosis. 2006. Cochrane Database.
19. Boyd J, Macklin E, Strunk R and DeBaun M. Asthma is associated with acute chest syndrome and
pain in children with sickle cell anemia. Blood. 2006;108 :2923-2927
20. Padman R and Henry M. The use of bilevel positive airway pressure for the treatment of acute
chest syndrome of sickle cell disease. Abstract. Del Med J.2004.76: 199-203
21. Myers J The Complete Respiratory Assessment Score accurately predicts outcomes in children
with acute RAD exacerbations. * Power Point presentation (Unpublished)
22. Graham L. Sickle Cell Disease: Pulmonary Management Options. Pediatric Pulmonology,
Supplement 26:191-193. 2004
23. Styles, L. A., M. Abboud, et al. (2007). Transfusion prevents acute chest syndrome predicted by
elevated secretory phospholipase A2.Br J Haematol 136(2): 343-4.
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Guideline Preparation
This guideline was prepared by the Evidence-Based (EB) Clinical
Decision Support Team in collaboration with content experts at
Texas Children’s Hospital and the Texas Children’s Pediatric
Associates. Development of this guideline supports the TCH Quality
and Patient Safety Program initiative to promote clinical guidelines
and outcomes that build a culture of quality and safety within the
organization.
ACS Content Expert Team
Gladstone Airewele MD, Pediatric Hematology/Oncology
Michele Mariscalco MD, Critical Care
Julie Katkin MD, Pulmonary Medicine
Joseph Allen MD, Emergency Medicine
Lee Evey, RT Respiratory Therapy
Suzanne Iniguez RT, Respiratory Therapy
Joy Hesselgrave RN, Nursing
Elizabeth Fredeboelling, RN
Tangula Taylor, RN
Shelley Oh, Pharm D.
EB Clinical Decision Support Team
Marilyn Hockenberry PhD, RN, PNP-CS, FAAN Co-Chair
Virginia Moyer MD, MPH, Co-Chair
Research Specialist
Mireya Paulina Velasquez MD
Development Process
This guideline was developed using the process outlined in the EB
Clinical Decision Support Manual (2007). The review summary
documents the following steps:
1.
Review Preparation
-PICO questions established
-Evidence search terms confirmed with content experts
2.
Review of Existing Internal and External Guidelines
- One published guideline from the Sickle Cell Disease Care
Consortium
- One published guideline from the ACCP on
Nonpharmacologic Airway Clearance Therapies
Search for Relevant Evidence
-Searched: Medline, EmBase, Cochrane, BIREME, Google
Scholar
3.
4.
Critically Analyze the Evidence
-Three systematic reviews from the Cochrane Database, 5
RCTs , 29 non-randomized studies, 16 review articles
5.
Summarize the Evidence by preparing the guideline, order sets
and interdisciplinary plan of care
-Materials used in the development of the guidelines, review
summaries and content expert team meeting minutes are
maintained in an Acute Ches Syndrome EB review manual
within the Center for Quality.
Study/systematic review with minor limitations - specifically
lacking in one of the above criteria
Study/systematic review with major limitations - specifically
lacking in several of the above criteria.
Published clinical guidelines evaluated for this review using the
AGREE criteria. The summary of these guidelines are found at the
end of this document. AGREE criteria uses a 1-4 point likert scale
to evaluate 23 questions evaluating: Guideline Scope and Purpose,
Stakeholder Involvement, Rigor of Development, Clarity and
Presentation, Applicability, and Editorial Independence. The higher
the score the more comprehensive the guideline.
This guideline specifically summarizes the evidence in support of or
against specific interventions and identifies where evidence is
lacking. The following categories describe how research findings
provide support for treatment interventions.
“Evidence that supports” the guideline (p.1) provides clear evidence
from more than one well-done randomized controlled trial (RCT)
(based on CASP criteria) that the benefits of the intervention exceed
harm.
“Evidence against” (p.1) provides clear evidence from more than
one well-done RCT (based on CASP criteria) that the intervention is
likely to be ineffective or that it is harmful.
“Evidence lacking” (p.1) indicates there is currently insufficient data
or inadequate data to recommend for or against specific intervention.
Recommendations
Recommendations for the guidelines were developed by a consensus
process directed by the existing evidence, content experts and patient
and family preference when possible. The Content Expert Team and
EB Clinical Decision Support Team remain aware of the
controversies in the management acute chest syndrome in children
with sickle cell disease. When evidence is lacking, options in care are
provided in the guideline and the order sets that accompany the
guideline.
Approval Process
Guidelines are reviewed and approved by the Content Expert Team,
EB Clinical Decision Support Team, EB Executive Steering Team,
Pharmacy and Therapeutics Committee and other appropriate
hospital committees as deemed appropriate for the guideline’s
intended use. Guidelines are reviewed and updated as necessary
every 2 years within the EB Clinical Decision Support Team at Texas
Children’s Hospital. Content Expert Teams will be involved with
every review and update.
Disclaimer
Guideline recommendations are made from the best evidence, expert
opinions and consideration for the patients and families cared for
within TCH/TCPA. The guideline is NOT intended to impose
standards of care preventing selective variation in practice that are
necessary to meet the unique needs of individual patients. The
physician must consider each patient’s circumstance to make the
ultimate judgment regarding best care.
Evaluating the Quality of the Evidence
The Critical Appraisal Skills Program (CASP) criteria were used
to evaluate the quality of articles reviewed. Application of the CASP
criteria are completed by rating each reviewed study or review as:
Strong study/systematic review - well designed, well conducted,
adequate sample size, reliable measures, valid results, appropriate
analysis, and clinically applicable/relevant.
___________________________________________________
© Evidence-Based Decision Support Team, Quality and Outcomes Center,
Texas Children’s Hospital; October 2007
6