Pulmonary Complication Of Sickle Cell Disease

1. Pulmonary Complication Of Sickle Cell Disease SalehAlharbiMD FAAP FCCP ABP SBP Assistant Professor of Pediatrics Omm Al-Qura University

2. Outlines • ACS • PHT • Plastic Bronchitis • Preoperative Management • Pulmonary Rehabilitation

3. Acute Chest Syndrome • Inclusion:all children and adolescents with sickle cell diseases • Definition: a new infiltrate on CXR, excluding atelectasis, plus one or more of the following : • tachypnea • fever > 38.5 • chest pain • cough • wheezing • hypoxemia (room air SaO2 3-5% points less than baseline)

4. Acute Chest Syndrome • Pulmonary infiltrates • sometimes with effusion • with one or more of the following: • Chest pain • 40% also have abdominal pain • Fever • Impaired oxygenation • May also have chills • Often preceded by vaso-occlusive crisis • high phospholipase A-2 levels

5. Acute Chest Syndrome • intravascular clogging • fat embolism • atelectasis • infection • thromboembolism

6. Infectious Causes • Staph aureus • Strep pneumoniae • Hemophilusinfluenzae • Klebsiellapneumoniae • Chlamydia • Mycoplasma • Viral most common

7. Causes of Acute Chest Syndrome

8. Pathogenesis Gladwin et al. Lancet 2000;355:1477

9. Vicious Cycle • Sickling worsens with hypoxemia, acidosis • Atelectasis causes vasoconstriction • sluggish flow and more occlusion • Chest pain causes splinting • under aeration and atelectasis • Narcotics for pain may decrease ventilation • increased atelectasis • increased PaCO2 increases acidosis

10. Co-morbidities • asthma • marked anemia • thrombocytopenia • pulmonary hypertension • cor pulmonale

11. One thing leads to another • Acute chest syndrome often recurs • Gradual scarring • Restrictive lung disease • Pulmonary hypertension • even without overt acute chest episodes • Corpulmonale • 20% of patients with ACS develop neurologic complications (often beginning with confusion)

12. Acute Chest Syndrome: Outcome • Complete recovery 91% • Weaned of supplemental O2 3.1±1.9 days • Hospital discharge 5.4±2.3 days • Chronic respiratory disease 3% • Death 6% Blood: 2004

13. Therapy of Acute Chest Syndrome • Oxygen • avoid excess which reduces erythropoiesis • Careful rehydration • maintain euvolemia • judicious use of furosemide often helpful • Pain control • narcotics • ketorolac • acetaminophen

14. Antibiotics • For the first 72 hours of admission, the patient should receive a third-generation cephalosporin (IV cefotaxime, 200mg/kg/day, divided q6–8h, max. 10g/day starting 24hr after the initial admission dose of ceftriaxone).

15. Beyond 72h, some may be switched to cefuroxime (75 -150mg/kg/day IV, divided q8h, max. 6g/day), as follows: • Mild pneumonia & stable Cefotaxime for 72h, then cefuroxime • Moderately severe pneumonia Continue cefotaxime • Severe pneumonia or unstable Cefotaxime + vancomycin60mg/kg/day, divided q6h; max. 4g/day

16. Children ≥ 5 years of age should be suspected of having mycoplasma pneumonia; • add Clarithromycin15mg/kg/day po divided q12h (max. 1g/day) or Erythromycin (40mg/kg/day, IV, divided q6h; max. 4g/day or po as estolate, divided q6-12h, max. 2g/day). • Use IV Clarithromycin in patients younger than 5 only if there is suspicion of mycoplasma. • Patients with a significant beta-lactam antibiotic allergy can be treated with • clindamycin (40mg/kg/day, IV, divided q6-8h; max. 3.6g/day); or 30mg/kg/day po (q6-8h max. 1.8g/day).

17. For children older than 4 years, consult a respiratory therapist for incentive spirometry: 10 breaths q1–2h when awake, or 5 breaths every 15 minutes

18. Therapy of Acute Chest Syndrome • Improve oxygen delivery • reduce % hemoglobin S • packed red cell transfusion – early on! • exchange transfusion if still worsening (rarely needed if transfused early) • bronchodilators • albuterol regardless of presence or absence of wheezing • non-invasive ventilation • endotracheal intubation • adequate PEEP • incentive spirometry

19. Therapy of Acute Chest Syndrome • Dexamethasone may shorten course • However, use of steroids associated with: • 1/3 of patients are readmitted • Increased risk of avascular necrosis • Pancreatitis

20. Therapy of Acute Chest Syndrome • Unproven therapies, but “seem to work” • Dornasealfa- inhaled • Nitric oxide • ECMO

21. Newer therapies • Dexamethasone0.3mg/kg IV q12h x 4 doses – Inhibition of inflammation, inhibit cytokine induction of adhesive molecules • Nitric oxide (NO) – Decrease pulmonary vascular resistance, improve pulmonary blood flow • Polaxamer 188 – Reduce blood viscosity, inhibit RBC adhesion to endothelium

22. Purified Poloxamer 188 for Treatment of Acute Vaso-occlusive Crisis of SCD Randomized Controlled Trial • Purified poloxamer188 may increase tissue oxygenation and thereby reduce inflammation,pain, and the overall duration of such painful episodes in patientswith SCD • Conclusions A decrease in the duration of painful episodesand an increase in the proportion of patients who achieved resolutionof the symptoms were observed when the purified poloxamer 188–treatedpatients were compared with the patients receiving placebo. JAMA. 2001;286:2099-2106

23. Options for Respiratory Failure • 1. Exchange transfusion • 2. Respiratory support • Conventional mechanical ventilation • High-frequency oscillatory ventilation • For ventilated patients repeated daily bronchoscopy with lavage and aggressive suctioning of bronchial casts • Nitric Oxide (NO) via mask or endotrachial tube • Extra Corporeal Membrane Oxygenation (ECMO) has been reported

24. Summary ( ACS) • Oxygen to correct hypoxia • • Respiratory therapy including use of incentive spirometry • • Antibiotic coverage (including community acquired organisms) • • Maintain euvolemia • • Pain management – avoid chest splinting and over sedation • • Bronchodilator therapy trial • • PRBC Tx if respiratory compromise

25. Pulmonary Hypertension in Sickle Cell Disease • Many Factors Contribute to Development of PAH in SC Disease • Repeated Episodes of Regional Pulmonary Hypoxia • Infection • Bronchoreactive lung disease • Chronic thromboembolism + fat embolism • Pulmonary fibrosis • Intravascular hemolysis with release of Hgb and arginine

26. Regional Pulmonary Hypoxia •  • Sickling,  Vascular adhesion, production of vasoactive substances •  • Reoxygenation followed by reperfusion injury •  • Progressive tissue damage with altered pulmonary vascular tone, vascular proliferation in the muscle wall and hypercoagulable state causing pulmonary thrombosis and progressive loss of the vascular bed •  • Obliterative Pulmonary Vasculopathy with pulmonary hypertension

27. Role of NO (Nitric oxide) • Produced by endothelial cells (blood vessels) • Has vasodilative and cytoprotective effects that counter the processes induced by hypoxia • However, in sickle cell disease, levels of both arginine (the substrate for NO) and NO are low, diminishing the benefits of NO • Why is NO low in Sickle Cell Disease? • Intravascular hemolysis

28. Depletion of NO in sickle cell anemia Sildenifil: Increase effect of NO on cellular function

29. Plastic Bronchitis In Acute Chest Syndrome • Plastic bronchitis is a rare disorder characterised by the formation of branching mucoid bronchial casts • Recently a high prevalence (72%) of plastic bronchitis, a condition associated with widespread mucous plugging of the tracheobronchial tree, has been reported in patients with ACS following flexible bronchoscopy

30. It is usually associated with underlying pulmonary diseases like bronchial asthma, allergic bronchopulmonaryaspergillosis, cystic fibrosis, bronchiectasis and at times other system diseases like congenital heart defects and sickle cell disease • Plastic bronchitis presenting as acute respiratory distress with wheezing, breathlessness, and cough, mimicking foreign body aspiration had been reported

31. Treatment of plastic bronchitis in acute chest syndrome of sickle cell disease with intratrachealrhDNase • S S Manna, J Shaw, S M Tibby, A Durward Arch Dis Child 2003;88:626–627

32. Plastic Bronchitis and the Role of Bronchoscopy in the Acute Chest Syndrome of Sickle Cell Disease • Chuanpit Moser, Eliezer Nussbaum and Dan M. Cooper Chest 2001;120;608-613

33. Chest radiographs of an 11-year-old boy with SCD obtained during an episode of ACS. Top: Before bronchoscopy, left lower lobe consolidation was evidenced by loss of cardiac and diaphragmatic silhouettes (small arrows). Bottom: After bronchoscopy, marked improvement was shown by reappearance of the aortic and left diaphragmatic borders (large arrows).

34. Chronic Pulmonary Disorders in Sickle CellDisease: Findings at Thin-Section CT’ • The main finding of our study is that significant pulmonary interstitial disease is present on thin-section CT scans of the lower lungs in 41% of these selected patients with SC disease. • Pulmonary interstitial disease was manifested by a patchy and predominantly basal distribution of interlobular septal thickening, panenchymalbands, pleural tags, dilated secondary pulmonary lobules, traction bronchiectasis, and architectural distortion. • Radiology 890 Volume 193 Number 3 2004

35. Future directions • Sildenafil reduces pulmonary hypertension • improves exercise endurance • Gardos channel blockers (not yet available) • improve intraRBC dehydration • improve markers of hemolysis • Arginine + hydroxyurea improves available nitric oxide, and may help vasculopathy

36. Preoperative Management • Preoperative transfusion improves morbidity • Highest risk of acute chest syndrome in first 48 hours after surgery • Outpatient surgery may be ill-advised • Better outcomes with laparoscopy

37. Incentive spirometry is indicated for older children with chest or back pain: 10 breaths q1–2h while awake, or 5 breaths every 15 minutes . • The hospital’s Child Life representative may also assist younger children with deep-breathing and blowing bubbles

38. Pulmonary Rehabilitation • The goals of pulmonary rehabilitation are to reduce symptoms, decrease the degree of disability, increase the patient's participation in physical and social activities and improve the patient's quality of life. • In addition to exercise training, pulmonary rehabilitation encompasses patient education, psychosocial and behavioral intervention and outcome assessment. American Thoracic Society Updates Statement 2007

39. Benefits of Pulmonary Rehabilitation • According to the report, studies have shown that pulmonary rehabilitation increases the level of exercise a patient can perform and decreases the degree of dyspnea for a given level of exercise. • According to the report, controlled trials have also shown that pulmonary rehabilitation is associated with a trend toward a decrease in the use of health care resources, including a reduction in the number and duration of hospitalizations.

40. Essential Components of Pulmonary Rehabilitation 1.Exercise training. • The report indicates that studies have shown a high level of exercise training (i.e., 60 percent of the maximal work rate, above the anaerobic threshold) produces greater improvement in maximal and submaximal exercise responses in patients with chronic obstructive pulmonary disease than does a low level of exercise training. • In patients who cannot train at 60 percent of their maximal work load for a prolonged period, interval training in the form of two to three minutes of high-intensity (60 to 80 percent of maximal exercise capacity) exercise is recommended.

41. Endurance training of the upper extremities is recommended in addition to endurance training of the lower extremities. • Most pulmonary rehabilitation programs use, alone or in combination, a stationary cycle or walking for building endurance in the legs.

42. 2.Patient education. According to the ATS statement, patient education is an integral component of a pulmonary rehabilitation program. • Important subject areas include breathing retraining (such as pursed-lip breathing and diaphragmatic breathing), techniques for energy conservation and the proper use of medications. 3.Psychosocial and behavioral intervention. Problems such as anxiety, depression and difficulties coping with chronic pulmonary disease can be addressed during pulmonary rehabilitation.