Sickle Cell Acute Chest Syndrome Jenny Kim MD Medical Director, Comprehensive Sickle Cell Program Rady Children’s Hospital San Diego Clinical Professor of Pediatrics UCSD School of Medicine

Disclosures NONE

Objectives: Acute Chest Syndrome How common is ACS and who gets it? What is ACS? What causes ACS? How do I know if a person has ACS? How is ACS treated?

Pulmonary complications of SCD Acute chest syndrome Asthma Pulmonary hypertension Blood clots/PE Obstructive sleep apnea Pulmonary fibrosis Chronic dyspnea PFT changes Am J Respir Crit Care Med. 2001; 164(11):2016 Postgrad Med J. 2003; 79(933): 384 Br J Haematol. 2005;129(4): 449

How common is ACS? Cooperative Study of Sickle Cell Disease (CSSCD) study period 1978-1998 - PURPOSE to describe natural history of SCD 4000 pts with SCD observed prospectively for >/=2 yrs ACS incidence 29% Occurs in up to 45% of SCD pts- recurrent in up to 80% Castro et al. Blood, 1994;84(2):643 N Engl J Med 2000;342: 1855-1865 N Engl J Med 2004;350: 886-895 N Engl J Med 1994;330: 1639-44 Blood 1997;89: 1787-92

How common is ACS? In adults, ACS develops 1-3 days after admission for VOC In children, ACS is admitting diagnosis Adults Children Incidence lower higher Severity greater less Mortality 9% 1% Rate of death per ACS episode 4.3% 1.1% National Acute Chest Syndrome Study Group N Engl J Med. 2000;342(25): 1855

Who gets ACS? 2nd most common cause of hospitalization for pts with SCD Almost half developed ACS during hospitalization for something else Increased ACS risk in children with asthma or tobacco exposure

Sean Fox, Pediatric EM Morsels 7/26/13 Who gets ACS? Increased ACS incidence in sickle cell pts with: HIGHER baseline hgb levels LOWER fetal hgb levels HIGHER baseline WBC Sean Fox, Pediatric EM Morsels 7/26/13

Mortality due to ACS Most common cause of death in pts with SCD One-fourth of SCD-related deaths due to ACS Death rate in pts with ACS: 1.8% in children, 4.3% in adults Adults with higher ACS rate -> higher mortality rate from all causes

What causes ACS? National Acute Chest Syndrome Study Group (NACSSG) evaluated 671 episodes of ACS in 538 patients Infection Asthma Vaso-occlusive pain episode Smoke exposure Postoperative complication Chronic hypoxemia Vichinsky et al. N Engl J Med. 2000;3432(25): 1855 Kokoska et al. L Pediatr Surg. 2004;39(6): 848

Vichinsky et al. N Engl J Med. 2000;3432(25): 1855 Infections Unknown cause in 30-46% Pulmonary infarction 16% Fat embolism +/- infection 9% Chlamydia pneumoniae infx 7% Mycoplasma pneumoniae infx 7% Viral infections 6% Mixed infections 4% Other pathogens 1% A.D.A.M. www.adam.com www.chlamydia-pneumoniae.org Vichinsky et al. N Engl J Med. 2000;3432(25): 1855

Vaso-occlusive pain episode Hypoventilation due to sedation from opioid pain meds Hypoventilation due to pain in chest, ribs, abdomen, back Pulmonary infarction

Post-operative complication Abdominal surgeries —> Cholecystectomy —> Splenectomy Chest wall surgery: port placement Pain - splinting, opioid sedation, hypoventilation Atelectasis Infection

Asthma Asthma increases risk for ACS in pts with SCD Pts with SCD and asthma 2-4x more likely to develop ACS with longer inpt stays and more frequent VOC painful episodes Bronchodilators help open reactive airways during ACS Smoke exposure increase hospitalization rates Pediatr Pulmonol. 2004;38(3): 229 Blood. 2006;108(9): 2923 Int J Environ Res Public Health. 2016;13(11) Epub 2016 Nov 12

Chronic hypoxemia Children with SCD increased risk for nighttime hypoxemia Nighttime hypoxemia associated with increased sickling and vaso-occlusive events and ACS Obstructive sleep apnea Oxygen by nasal cannula or bipap

Diagnosis of ACS New infiltrate on CXR Chest pain Fever and one of the following sxs: Chest pain Fever Increased work of breathing Cough Hypoxia

Acute management Hydration - not too little, not too much Optimal pain control to minimize hypoventilation Supplemental oxygen to keep sats >92-95% Incentive spirometry Bronchodilators Steroids?

Acute management Labs: CBC, retic, type/cross, blood cx, liver and renal chemistries Antibiotics to cover for community acquired pneumonia and mycoplasma/chlamydia pneumoniae - ceftriaxone and azithromycin Simple vs exchange blood transfusion

Long term management Monitor PFTs Preventative asthma management Outpatient pulmonary referral Supplemental oxygen for nighttime hypoxia Chronic transfusion therapy Hydroxyurea Stem cell transplant

Summary ACS is the 2nd most common cause of hospitalization in pt with SCD and most common cause of death. ACS is caused by increased sickling of RBCs in the pulmonary blood vessels causing vaso-occlusion and injury to the lungs. The trigger for ACS is often not identified. In kids, it is often infection and VOC events, and pts often already hospitalized for something else.

Summary Diagnosis of ACS includes new infiltrate on CXR and either chest pain, fever, respiratory distress, hypoxia. Acute treatment includes gentle hydration, oxygen for hypoxia, pain control, incentive spirometry, bronchodilator, antibiotics to cover community acquired pneumonia and mycoplasma/chlamydia pneumoniae, and blood transfusion. Recurrence in up to 80% so long term management directed toward preventing recurrence: vaccines, asthma management, monitoring PFTs, pulmonary referral, hydroxyurea, stem cell transplant