Treatment of Acute Chest Syndrome Incentive Spirometry

Other Lung Diseases Mark J. Rosen, MD, FCCP Chief, Divisions of Pulmonary, Critical Care and Sleep Medicine North Shore University Hospital and Long Island Jewish Medical Center Professor of Medicine Albert Einstein College of Medicine Disclosure Information Mark J. Rosen, MD, FCCP I have no conflicts of interest with the topics that I am going to discuss. Other Lung Diseases • Pulmonary complications of sickle cell disease • Pulmonary complications of liver disease • Oxygen toxicity • Radiation-induced lung disease • Smoke inhalation • Carbon monoxide • Methemoglobinemia Sickle Cell Hemoglobinopathies • Sickle cell anemia (hemoglobin SS) affects 1/650 AfricanAmericans • In the US, also affects Latinos from the Caribbean, Central America, South America Sickle Cell Disease Pathogenesis Bunn HF. N Engl J Med 1997; 337:762-769 Sickle Cell Disease Pathogenesis Platt OS. N Engl J Med 2000;342:1904-7 Sickle Cell Anemia Pathogenesis • Hemoglobin polymerization – Deoxygenation: degree and duration – Hemoglobin concentration in RBC: cellular dehydration – Inversely proportional to hemoglobin F Sickle Cell Disease Pathogenesis • Microvascular occlusion • Increased adhesion of RBCs and WBCs to vascular endothelium • Vasoconstriction: endothelin-1 expressed after contact with sickled RBCs • Activation of coagulation system: thrombocytosis, procoagulant RBC lipids • NO dysregulation following release of arginine and Hgb from hemolysis Sickle Cell Disease Role of NO Hemolysis Release free hemoglobin  Scavenge NO Release RBC arginase Steudel W. Anesthesiology 1999;91:1090-121 Griffiths. JD. N Engl J Med 2005;353:2683-2695 Sickle-Cell Disease Pulmonary syndromes • Acute chest syndrome (ACS) • Fat embolism syndrome • Chronic restrictive lung disease with pulmonary hypertension CPC. N Engl J Med Sickle-Cell Disease Acute Chest Syndrome • Chest pain, fever, cough, often during painful crisis • CXR: multilobe or lower lobe opacities; pleural effusion in 15% Acute Chest Syndrome Pathogenesis • Pulmonary infarction – In situ thrombosis – Thromboembolism – Fat embolism • Thoracic bone infarction  pain  atelectasis and pneumonia • Pulmonary infection The most common pathogen identified in patients with acute chest syndrome is: A. B. C. D. S. pneumoniae H. influenzae C. pneumoniae Influenza virus 1 The most common pathogen identified in patients with acute chest syndrome is: A. B. C. D. S. pneumoniae H. influenzae C. pneumoniae Influenza virus 1 Acute Chest Syndrome Causes and Outcomes • 671 episodes in 538 patients • Extensive diagnostic evaluation – Blood cultures – Nasopharyngeal cultures – FOB: cultures, fat stains – PCR for Chlamydia – Acute and convalescent sera: mycoplasma, EB virus, Chlamydia, parvovirus Vichinsky EP et al. N Engl J Med 2000;342:1855-65. Acute Chest Syndrome Etiology* Fat embolism Chlamydia Mycoplasma Virus Bacteria Mixed inf Legionella 0 4 10 20 30 40 50 60 70 25 30 44 43 48 59 *Established in 364/670 episodes Vichinsky EP et al. N Engl J Med 2000;342:1855-65 Acute Chest Syndrome Pathogens Identified Chlamydia Mycoplasma RSV Other virus S. aureus S. pneumoniae H. flu CMV Influenza A Legionella 71 51 26 24 12 11 5 4 4 4 0 20 40 60 80 Vichinsky EP et al. N Engl J Med 2000;342:1855-65 ACS in Patients > 20 years • 22% required mechanical ventilation • Predictors: > 4 lobes involved, platelets < 200,000, history of cardiac disease • 9% died Vichinsky EP et al. N Engl J Med 2000;342:1855-65. Acute Chest Syndrome Neurologic Complications • 22% of adults developed neurologic disorders – Altered mental status – Seizures – Neuromuscular – Anoxic injury – Hemorrhage – Infarction Vichinsky EP et al. N Engl J Med 2000;342:1855-65. Acute Chest Syndrome Treatment • • • • • • RBC transfusion Analgesics Hydration Oxygen Antibiotics Incentive spirometry Sickle Cell Disease Potential Therapies Pulmonary Hypertension in Sickle Cell Disease • 195 adults with sickle cell disease • Doppler-defined PH in 32% • Associated with – Hx cardiovascular or renal complications – Increased systolic BP – High LDH (hemolysis?) – High alkaline phosphatase – Low transferrin levels – Increase risk of death (rate ratio 10.1) Gladwin MT, et al. N Engl J Med 2004;350:886-895 Pulmonary Hypertension in Sickle Cell Disease Gladwin MT, et al. N Engl J Med 2004;350:886-895 Pulmonary Hypertension in Sickle Cell Disease Gladwin MT, et al. N Engl J Med 2004;350:886-895 Liver-Lung Syndromes • • • • Hepatopulmonary syndrome Portopulmonary hypertension Alpha-1 antitrypsin deficiency Hepatic hydrothorax Hepatopulmonary Syndrome • Triad: liver disease, hypoxemia, “intrapulmonary vascular dilatations” (precapillary and capillary) • “Diffusion-perfusion” disorder • High cardiac output • Anatomic shunts: pleural spider nevi and portopulmonary anastamoses (platypnea) Hepatopulmonary Syndrome Mazzei JAM. PCCU Update Lesson 1, Vol 14 Hepatopulmonary Syndrome • Pathogenesis of vascular dilatations: abnormal vascular mediators leaving the liver enter the lungs remodel pulmonary vessels • Increased NO production  vasodilation, CO Hepatopulmonary Syndrome Diagnosis • Clinical: liver disease (15-20% of patients with cirrhosis have HPS) • Criteria: – Portal hypertension – A-a DO2 >15 mm Hg – Vascular dilatation • Echocardiographic: air bubbles appear in left atrium 3-6 beats after visualization in right atrium, or • Nuclear: Radionucleide appears in brain 4-6 cycles after injection Hepatopulmonary Syndrome Role of NO Methylene blue decreased cGMP  vasoconstriction   CO,  PaO2 X X Steudel W. Anesthesiology 1999;91:1090-121 Griffiths. JD. N Engl J Med 2005;353:2683-2695 Portopulmonary Hypertension • Occurs in 1%-2% of patients with cirrhosis and portal hypertension • Indistinguishable from IPAH • Usually does not improve after liver transplantation Hepatic Hydrothorax • Difficult-to-control pleural effusions in patients with ascites • Probably due to congenital anatomic defects in the diaphragm • Pleural fluid almost identical with ascites • Typically transudate, right>left • Empyema may occur in patients with peritonitis Hepatic Hydrothorax Treatment is difficult • Thoracentesis: fluid reaccumulates • Chest tube: volume and electrolyte depletion • Pleurodesis: usually unsuccessful • Surgical repair of diaphragm: few centers have experience • Peritoneovenous shunts: Pleural fluid pressure < venous pressure Hepatic Hydrothorax Treatments • Transjugular intrahepatic portosystemic shunt (TIPS) • Liver transplantation Which statement about pulmonary oxygen toxicity is true? A. The histopathologic findings are specific for that condition B. The airways are usually not affected C. FiO2 < 0.6 has been shown to be nontoxic D. The lung is the most vulnerable organ to oxygen radical damage 5 Which statement about pulmonary oxygen toxicity is true? A. The histopathologic findings are specific for that condition B. The airways are usually not affected C. FiO2 < 0.6 has been shown to be nontoxic D. The lung is the most vulnerable organ to oxygen radical damage 5 Oxygen Radicals • O2-, H2O2, OH-are produced by stepwise reduction of O2 to water • Beneficial roles – used by neutrophils for phagocytosis and killing bacteria – Mediate vascular tone by interactions with NO Oxygen Radicals Toxicity • Cell membrane damage increased cell permeability • Lysosomal membrane damage  releases proteolytic enzymes • Inactivates cell enzymes • Damages DNA • Recruits neutrophils Oxygen Toxicity • Tracheobronchitis • Damage to type I pneumocytes increased capillary permeability • Hyaline membrane formation, type II pneumocyte proliferation, fibrosis Which of the following increases the risk of developing pulmonary oxygen toxicity? A. B. C. D. Bleomycin Prior exposure to inhaled oxygen Endotoxin Inhaled tobramycin 6 Which of the following increases the risk of developing pulmonary oxygen toxicity? A. B. C. D. Bleomycin Prior exposure to inhaled oxygen Endotoxin Inhaled tobramycin 6 Modulators of Lung Injury • Protective – Prior exposure to high FiO2 – Endotoxin (experimental) • Additive/synergistic – Drugs: bleomycin, nitrofurantoin, mitomicin, amiodarone – NO + O2 ONOO- Radiation Pneumonitis • Symptomatic disease in 7% • Injury to type II pneumocytes, capillary endothelial cells  cytokine response  recruits immune cells  more inflammation  fibrosis All of the following influence the severity of radiationinduced lung injury, except: A. B. C. D. Type of malignancy treated Daily and total dose of radiation Concomitant chemotherapy Withdrawal of corticosteroids 7 All of the following influence the severity of radiationinduced lung injury, except: A. B. C. D. Type of malignancy treated Daily and total dose of radiation Concomitant chemotherapy Withdrawal of corticosteroids 7 Radiation Pneumonitis Influences • Irradiated volume of lung tissue • Total dose – <30 Gy: well tolerated – >40 Gy: radiographic changes – >50 Gy: symptomatic injury • Fraction size • Prior irradiation • Chemotherapy • Withdrawal of corticosteroids Radiation Pneumonitis • • • • Latent period up to six months Nonspecific symptoms Chest film may be typical Radiographic changes may occur outside the radiation field Radiation Pneumonitis in the “Nonirradiated Lung” • 6 women received RT for breast cancer (mean dose 6,560 cGy) • Recurrent and migrating lung opacities outside the radiation field 6 to 17 months later • BAL (2 patients): lymphocytosis • Lung biopsy (5 patients): BOOP Arbetter KR, et al. Mayo Clin Proc 1999;74:27-36 Radiation Fibrosis • Usually occurs 6 months to 2 years after exposure • Usually stable after 2 years • Mediastinal fibrosis: SVC syndrome, constrictive pericarditis • Bronchiectasis, pleural thickening Smoke Inhalation Clinical Syndromes • • • • • Inhaled toxins CO poisoning Thermal injury Airway disease Pneumonia A 23-year-old man is brought to the emergency room after rescue from a burning building. He has secondand third-degree burns over 15% of his body, including his face. He is conscious, but in mild respiratory distress. Which test is least likely to be helpful in his immediate management? A. B. C. D. Arterial blood gas Carboxyhemoglobin level Chest radiograph Flexible laryngoscopy Which test is least likely to be helpful in his immediate management? A. B. C. D. Arterial blood gas Carboxyhemoglobin level Chest radiograph Flexible laryngoscopy Smoke Inhalation Thermal injury • Larynx: edema, spasm • Bronchi: inflammation, edema, spasm, hypersecretion, impaired mucociliary function • Does not usually affect distal airways or alveoli • CXR usually normal initially Bronchoscopy shows moderate ulceration and edema of the larynx and bronchi. Which of the following is most likely to benefit this patient? A. B. C. D. Corticosteroids Broad-spectrum antibiotics Continuous positive airway pressure Endotracheal intubation 10 Bronchoscopy shows moderate ulceration and edema of the larynx and bronchi. Which of the following is most likely to benefit this patient? A. B. C. D. Corticosteroids Broad-spectrum antibiotics Continuous positive airway pressure Endotracheal intubation 10 Burn Injury Mortality • Review of all patients with burn injuries admitted to MGH and Shriners Burns Institute, 1990-1994 • Three risk factors for death: – Age > 60 years – Body-surface area burn > 40% – Inhalation injury Ryan CM, et al. N Engl J Med 1998;338:362-6 Burn Injury Mortality Risk factor Inhalation injury only Inhalation + > 40% burn Inhalation + > 60 years All three Mortality Rate 5/112 (4%) 21/79 (27%) 12/31 (39%) 21/22 (95%) Ryan CM, et al. N Engl J Med 1998;338:362-6 Burn Injury Mortality Risk factors 0 1 2 3 Mortality Rate 3/1314 (0.2%) 10/218 (5%) 33/111 (30%) 21/22 (95%) Ryan CM, et al. N Engl J Med 1998;338:362-6 Smoke Inhalation Thermal injury • No role for routine corticosteroids • Pneumonia is a common cause of death – Pseudomonas aeruginosa – H. simplex tracheobronchitis Carbon Monoxide Poisoning • CO produced by incomplete combustion + decreased FiO2 • Common scenarios: – Fires – Coal, kerosene and wood-burning stoves in well-insulated homes – Portable heaters Carbon Monoxide Poisoning • CO affinity for Hgb 200x greater than O2 • Shifts oxyhemoglobin dissociation curve to the left • PaO2 may be normal, but CaO2 is reduced  tissue hypoxia • Signs of poisoning: CNS, cardiac, lactic acidosis Carbon Monoxide Toxicity Acute symptoms after exposure in 196 patients • • • • • Headache Dizziness Weakness Nausea Confusion 91% 77% 53% 47% 43% • • • • • Dyspnea Visual Chest pain LOC Abd pain 40% 25% 9% 6% 5% Ernst AE. N Engl J Med 1998;339:1603-8 Carbon Monoxide Poisoning Diagnosis • Increased carboxyhemoglobin level • Pulse oximetry cannot distinguish oxyhemoglobin from carboxyhemoglobin (“pulse oximetry gap”) Ernst AE. N Engl J Med 1998;339:1603-8 Carbon Monoxide Toxicity Delayed Neuropsychiatric Syndrome • Cognitive and personality changes, parkinsonism, incontinence, dementia, psychosis • May occur days or weeks after exposure • Recovery within one year in 50-75% • Most commonly involves globus pallidus and deep white matter Ernst AE. N Engl J Med 1998;339:1603-8 Carbon Monoxide Poisoning Diagnosis and Treatment • Asymptomatic, CO < 20%: no Rx • Symptoms, CO > 20 %: 100% O2 • Hyperbaric O2 in severe cases (coma, cardiac ischemia, arrhythmia) • Hyperbaric O2 reduces risk of cognitive sequelae (N Engl J Med 2002;347:1057) Methemoglobin • Product of oxidation of Fe++ to Fe+++ • MetHb has higher affinity for oxygen, shifts oxyhemoglobin curve to the left • Oxidant drugs – Metaclopramide – Dapsone – Sulfonamides – Local anesthetics – Nitrates Methemoglobinemia  Measured SpO2  “Functional” SpO2 Barker SJ, et al. Anesthesiology 1989;70:112-117 Hurford, et al. N Engl J Med 2004;351:380-387