Pulmonary Complication Of Sickle

Cell DiseaseSaleh Alharbi MD FAAP FCCP

ABP SBPAssistant Professor of Pediatrics

Omm Al-Qura University

Outlines ACS PHT Plastic Bronchitis Preoperative Management Pulmonary Rehabilitation

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)

Acute Chest Syndrome Pulmonary infiltrates

sometimes with effusion with one or more of the following:

Chest pain 40% also have abdominal pain

Fever Impaired oxygenationMay also have chills

Often preceded by vaso-occlusive crisis• high phospholipase A-2 levels

Acute Chest Syndrome

intravascular clogging fat embolism atelectasis infection thromboembolism

Infectious Causes

Staph aureus Strep pneumoniae Hemophilus influenzae Klebsiella pneumoniae Chlamydia Mycoplasma Viral

most common

Causes of Acute Chest Syndrome

Pathogenesis

Gladwin et al. Lancet 2000;355:1477

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

Co-morbidities

asthma marked anemia thrombocytopenia pulmonary hypertension cor pulmonale

One thing leads to another

Acute chest syndrome often recurs Gradual scarring Restrictive lung disease Pulmonary hypertension

even without overt acute chest episodes Cor pulmonale 20% of patients with ACS develop neurologic

complications (often beginning with confusion)

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

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

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).

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 +

vancomycin 60mg/kg/day, divided q6h; max. 4g/day

Children ≥ 5 years of age should be suspected of having mycoplasma pneumonia; add Clarithromycin 15mg/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).

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

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

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

Therapy of Acute Chest Syndrome

Unproven therapies, but “seem to work” Dornase alfa- inhaled Nitric oxide ECMO

Newer therapies Dexamethasone 0.3mg/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

Purified Poloxamer 188 for Treatment of Acute Vaso-occlusive Crisis of SCD

Randomized Controlled Trial

Purified poloxamer 188 may increase tissue oxygenation and thereby reduce inflammation, pain, and the overall duration of such painful episodes in patients with SCD

Conclusions  A decrease in the duration of painful episodes and an increase in the proportion of patients who achieved resolution of the symptoms were observed when the purified poloxamer 188–treated

patients were compared with the patients receiving placebo.

JAMA. 2001;286:2099-2106

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

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

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

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

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

Depletion of NO in sickle cell anemia

Sildenifil:Increase effect of NO on cellular function

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

It is usually associated with underlying pulmonary diseases like bronchial asthma, allergic bronchopulmonary aspergillosis, 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

Treatment of plastic bronchitis in acute chest syndrome of sickle cell disease with intratracheal rhDNase S S Manna, J Shaw, S M Tibby, A Durward Arch

Dis Child 2003;88:626–627

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

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).

Chronic Pulmonary Disorders in Sickle Cell

Disease: 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

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

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

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

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

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.

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.

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.

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.