Clinical Pathological Conference

1. Clinical Pathological Conference 三軍總醫院 小兒部 黃文欽/蔡明志大夫/華一鳴大夫

2. Present illness • A one day-old-male infant was brought to our hospital due to rapid breathing and cyanotic lip • This baby was a product of 3.1 kg to a primiparous mother through a normal spontaneous vaginal delivery after 40 weeks of gestation • The dyspnea was apparent soon after birth and was associated with lip cyanosis • The apgar score was 7 at 1 minute and 9 at 5 minutes, respectively • Other than these symptoms there were no fever, tachycardia, etc. Prenatal history was not available

3. Physical examinations • An acutelyill looking baby • Vital sign: PR: 150/ min RR: 66-74 /min BT:36‘C • HEENT: a symmetric head and face, and opened anterior fontanel • Chest: symmetric expansion. The breathing sound was generally coarse without rales or wheezing, a mild subcostal retraction • Heart: unremarkable, no murmur or thrill • Abdomen: soft and flat. The liver was palpable by 3 fingerbreadths • Extremities and skin:unremarkable

4. Hospital course • After admission he was placed on oxygen mask • The laboratory data done on day one as follow: • ABG: pH 7.3, pCO2 40.6 mmHg, pO2 24.8 mmHg, HCO3 19.1 mmol/l ( mixedmetabolic and respiratory acidosis ) • Na 142 mM/l, K 5.1 mM/l Cl 106 mM/l • The blood sugar was 45 mg/dl • Cr: 0.8mg/dl • Chest X-ray film on the next day showedground glass appearanceof the lungandatelectasis in the right lower lung field

6. Hospital course D3 • On hospital day (HD) 3, tachycardia was noted in addition to tachypnea • A mild jaundice was also noted • Breathing sound was weak without rales • Volume decrease of the right hemithorax with hyperinfiltration of the left lung, dextroposition without cardiomegaly, and right lower lung field lesions • Oxygen saturation became 74% and blood pressure rose to 75/39 mmHg from 49/20 mmHg after dopamine infusion

8. Hospital course D4 • He was placed on ventilator on HD 4, with FiO2 0.5, after which ABGA revealed pH 7.26, pO2 124 mmHg, pCO2 45.5 mmHg, HCO3 20.6mmol/l, O2 saturation 95% and base excess -6mmol/l( mixedmetabolic and respiratory acidosis ) • Antibiotics was also given because of persistent right lower lobe lesion • Respiratory difficulty did not improve. And his urine output became gradually decreased (shock)

9. Hospital course D4 • Blood glucose level remained in the range of 50-58mg/dl • The patient had no fever or jaundice • Urine culture grew nothing • CxR showed hypervascularity (pulmonarycongestion) in addition to persistent right lower lobe shadow and lung infiltration

11. Hospital course D6 • The respiratory difficulty was still present, and pneumonic infiltration was noted in the left lung • ABGA showed pH 7.33, pCO2 44 mmHg, pO2 66.2 mmHg, HCO2 23.8mmol/l, O2 saturation 90% and base excess -1.7 mmol/l (compensated respiratory acidosis) • He was still on ventilator with FiO2 0.6, RR 15 and PIP 18. • WBC count was 40,000/cmm with 84%neutrophils

12. Hospital course D7 • Rhonchi became manifest, and the breathing sound decreased in the right lower lobe • Emphysematous picture was seen in the left lung field • Chest ultrasonography showed right lower lobe collapse and suggested pneumonia

13. Laboratory data • WBC:2720/cmm (normoblast 2%, seg 57, lymphocyte 30%, monocyte 10%, band form 3%) • RBC 4.99x106/cmm, hemoglobin 16.9gm/dl, hematocrit 51%, platelet 150,000/cmm • Ca 8.1 mg/dl, phosphorus 7.4 mg/dl, ionized Ca 3.3 mg/dl • lactic dehydrogenase 1088 IU/I, creatine phosphokinase 820 IU/I • bilirubin 7.7 mg/dl • Prothrombin time was 38.7 sec(19%) and activated PTT 267 sec

14. Hospital course D8 • The baby started to show arrhythmia • The blood gas data became aggravated and no self respiration (respiratoryfailure) was noted • Oxygen saturation of blood became progressively worse despite ventilator setting of FiO2 0.85 • Chest wall retraction and pale wet skin were noted. The baby died on hospital day 9

16. Day 1 Day 4 Day 6 Day 7 PH 7.37.26 7.33 PO2 24.8 124 66.2 PCO2 40.6 45.5 44 HCO3 19.1 20.6 23.8 SaO2 95% 90% Glucose 45 50-58 WBC 40,0002720 N/L/M 84% 57/30/10 Hgb 16.9 Hct 51% T/F Ca 8.1/3.3 PO4 7.4 LDH 1088 CPK 820 PT/PTT 38.7/267

17. Day 2 Day 3 Day 4 Day 9

18. Major problems • Respiratory distress • Atelectasis of right lung with dextroversion • Multiple cyst-like structure over the right lung field • Shock: BP down , decreased urine output, metabolic acidosis, tachycardia, pale wet skin

19. Minor problems • Tachycardia • Jaundice • Leukocytosis then leukopenia • Prolonged PT/PTT • Hypocalemia • High level of LDH and CPK • Emphysematous change of left lung field

20. Questions • Birth history: is there Hx of birth trauma during delivery? Meconiusm-stained? • Chest CT scan or MRI • Echocardiography, chest sonography, abdominal sonography • Had EKG been done and the results • Blood culture, CRP, CSF culture, virus culture, sputum culture • Had bronchoscopy been done and the results

21. Causes of respiratory distress in full-term neonate Common Meconium aspiration pneumonia Congenital heart disease Transient tahcypnea Persistent fetal circulation Congenital pneumonia Uncommon Pneumothorax Congenital anomalies Pneumopericardium Polycythemia Vocal cord paralysis Pleural effusion Severe anemia Pulmonary hypoplasia Pulmonary lymphangiectasia

22. Causes of Respiratory distress from Congenital Heart Disease Age of Onset Cause At birth HLHS Venous overload lesions: Severe tricuspid or pulmonary insufficiency Large systemic AV fistula First wk TGA PDA in small premature infants HLHS(with more favorable anatomy) TAPAR, particular with pulmonary venous obstruction Others: Systemic AV fistula Critical AS or PS

23. Causes of respiratory distress in full-term neonate Congenital anomalies Tracheoesophageal fistula Choanal atresia Diaphragmatic hernia Eventration of diaphragm Cystic adenomatoid malformation Lobar emphysema Pierre-Robin syndrome Thyroid goiter Congenital pulmonary cyst Chylothorax Vascular rings and slings Arteriovenous malformation Subglottic stenosis

24. Causes of Atelectasis in full-term neonate External compression of pulmonary parenchyma Pleural effusion, pneumothorax, intrathoracic tumors, lobar emphysema, diaphragmatic hernia, cystic adenomatoid malformation Endobronchial obstruction Enlarged LN, tumor, cardiac enlargement, foreign body, mucoid plug, broncholithiasis Intraluminal obstruction Foreign body, granulomatous tissue, pulmonary abscess Intrabronchiolar obstruction Bronchiolitis, interstitial pneumonitis, pneumonia Respiratory compromise or paralysis Neuromuscular abnormalities, osseous deformitis

25. Causes of multiple cyst-like lesions in lung • Congenital pulmonary cysts • Acquired lung cysts (pneumatoceles) • Congenital cystic adenomatoid malformation • Congenital bronchogenic cysts • Neurenteric duplication cysts

26. Shock • Shock is characterized by inadequate circulatory provision of oxygen, leads to lactic acidosis • Shock is a progressive process • Hypovolemic and septic shock are the most common causes of shock in children • Cardiogenic shock maybe seen in neonates with congenital heart disease

27. Causes of shock Septic Bacterial, Viral, Fungal Cardiogenic Ischemic insult Cardiomyopathy Congenital heart disease Distributive Neurogenic Anaphylaxis Toxins Allergic reactions Hypovolemic Enteritis, Hemorrhage Extensive burns Diabetes insipidus Adrenal insufficiency Obstructive Tension pneumothorax Pericardial tamponade

28. Serious Systemic Illness in Newborns: Differential Diagnosis of Neonatal Septic Shock Cardiac Metabolic Congenital: Hypoplastic left heart Hypoglycemia syndrome, other structural Dx, PPHN Adrenal disorders: Adrenal Acquired: Myocarditis, hypovolemic or hemorrhage, insufficiency, PPHN congenital hyperplasia Gastrointestinal Inborn errors of metabolism Necrotizing enterocolitis Neurologic Spontaneous GI perforation ICH: spontaneous, child abuse Structural abnormalities Hypoxic-ischemic encephalopathy Hematologic Neonatal seizures Neonatal purpura fulminans Infant botulism Immune-mediated thrombocytopenia Respiratory Immune-mediated neutropenia Respiratory distress sydrome Severe anemia Aspiration pneumonia Malignancies(congenital leukemia) Lung hypoplasia Hereditary clotting disorders Tracheoesophageal fistula TTNB

29. Serious Systemic Illness in Newborns: Differential Diagnosis of Neonatal Sepsis Infection Bacteremia or meningitis (Streptococcus pneumonia, Haemophilus influenza type b, Neisseria meningitidis) Viral illness (influenza, enteroviruses, hemorrhagic fever group, HSV, RSV, CMV, EBV) Encephalitis (arboviruses, enteroviruses, HSV) Rickettsiae (Rocky Mountain spotted fever, Ehrichia, Q fever) Syphilis Vaccine reaction (pertussis, influenza, measles) Toxin-mediated reaction (toxic shock, staphylococcal scalded skin syndrome) Pneumonia (bacterial, virus, mycobacteria, fungi, allergic reaction)

30. Causes of Cardiogenic shock During the 1st week of newborns Arteriovenous malformation Hypoplastic left heart syndrome Coarctation of aorta Interruption of aortic arch Aortic stenosis Transient myocardial ischemia

31. Possible Diagnosis Respiratory distress+ Atelectasis+ multiple cyst-like lesions in lung • Cystic adenomatoid malformation Respiratory distress+ Atelectasis • Pulmonary hypoplasia • Lobar emphysema • Diaphragmatic hernia Respiratory distress+ Shock • Hypoplastic left heart syndrome • TAPAR • Congenital pneumonia with septic shock

32. Congenital Cystic Adenomatoid Malformation • Congenital cystic adenomatoid malformation of the lung is anuncommon cause of respiratory distress in neonates and infants • Nevertheless, it is one of the most common pulmonary congenital anomalies • It consists of hamartomatous or dysplastic lung tissue mixed with more normal lung and usually confined to one lobes • It is characterized by a multicystic mass of pulmonary tissuewith an abnormal proliferation of bronchial structures

33. Congenital Cystic Adenomatoid Malformation • The lesion is a type of hamartoma with cysts structure and rarely may have malignant change • Associated malformations are present in about 20% of affected infants, like renal agenesis, jejunal atresia, diaphragmatic hernia, hydrocephalus, and skeletal Dx

34. Congenital Cystic Adenomatoid Malformation • Among infants in whom the malformation isdiagnosed postnatally, 50% to 75% will have someform of respiratory distress or compromise, including tachypnea,retractions, and cyanosis • The postnatal diagnosis is made with plain chest radiography,which demonstrates multiple air-filled thin-walled cysts thatvary in size

35. Congenital Cystic Adenomatoid Malformation • Type I is composed of variable-size cysts, with at least onedominant cyst (>2 cm in diameter) and this isthe most common (75%) form • A type II congenital cystic adenomatoid malformation is composedof smaller, more uniform cysts less than 1 cm in diameter (10%to 15% of all congenital cystic adenomatoid malformations) • A type III congenital cystic adenomatoid malformation is a solidmass composed of bronchoalveolar microcysts

36. Type I congenital cystic adenomatoid malformation. • Anteroposterior and (b) lateral chest radiographs of • a newborn show a multicystic mass occupying the right • hemithorax (note the variable size of the cysts, some of • them >2 cm)

37. Type II congenital cystic adenomatoid malformation. (a) Anteroposterior chest radiograph of a newborn shows a heterogeneous bubbly mass in the left lung displacing mediastinal structures to the right. (b) Coronal T1-weighted image in the same patient shows cysts (arrows) smaller than 2 cm in diameter

38. Type III congenital cystic adenomatoid malformation. Anteroposterior chest radiograph of a premature girl weighing 700 g shows an irregular microcystic mass affecting the left lung and displacing the mediastinum to the right. There is an associated dextrocardia

39. Congenital Cystic Adenomatoid Malformation • In severe cases, thelung may be hyperexpanded, with mediastinal shift, a flat hemidiaphragm,and herniation of the lung to the contralateral side • CT canbe useful for characterizing congenital cystic adenomatoid malformationby showing its location and extent • The treatment of choice is lobectomy as soon as possible after delivery • In infants subjected to early lobectomy, PPHN secondary to lung hypoplasia has been successfully managed with ECMO

40. Pulmonary Hypoplasia • Pulmonary hypoplasia is defined as deficient or incomplete developmentof the lungs • It is characterized by the presence of bothbronchi and alveoli in an underdeveloped lobe • It is caused by factors directly or indirectly compromising the thoracic space available for lung growth, such as a congenital diaphragmatic hernia, throacic dystrophy, pleural effusions with fetal hydrops, and cystic adenomatoid malformation • Intrathoracic causes, such as a congenital diaphragmatic hernia, are the most common

41. Pulmonary Hypoplasia • The most common manifestation is early respiratory distressafter birth, cyanosis, tachypnea, hypoxia, hypercapnea, andacidosis • Plain radiographs demonstrate decreased aeration of the affectedhemithorax (more frequent in the right lung) and a small thoraciccage

42. Pulmonary Hypoplasia • A common finding is a displacement of the mediastinum to theside of the hypoplasia • In some cases, a cystic appearance is encountered

44. CxR of a 7-month-old infant shows opacity of the left hemithorax and small left lung (arrows) with ipsilateral displacement of the mediastinum, secondary to repaired Bochdaleck hernia

45. Lobar Emphysema • Congenital lobar emphysema is characterized by progressive overdistentionof a lobe, sometimes two lobes • The most commonly affected lobe is the left upper lobe, followedby the middle lobe • Congenital lobar emphysema maybe associated with other anomalies (cardiovascular system isinvolved in 12%–14%)

46. Lobar Emphysema • Most patients become symptomatic during the neonatalperiod, most before 6 months of age • Respiratorydistress is the most common symptom at presentation, signs range from mild tachypnea and wheeze to severe dyspnea with cyanosis • Diagnosisis obtained by means of chest radiography and CT, which showhyperinflation of the segment or lobe affected

48. Diaphragmatic Hernia • Herniation of abdominal contents into the thoracic cavity • Esophageal hiatus-hiatal • Paraesophageal • Morgagani-retrosternal • Bochdalek-posterolateral • Congenital diaphargmatic hernia=Bochdalek • Profound respiratory distress in the neonatal period • Significant mortality (40-50%)

49. Diaphragmatic Hernia • Severe respiratory distress within 1st hour of life • A small group will present beyond the neonatal period • Absence of breath sounds and shift of heart sounds • CxR is usually diagnostic • The lateral view frequently demonstrate the posterior portion of diaphragm

50. Diaphragmatic Eventration • A thinned diaphragmatic muscle producing elevation of the entire hemidiaphragm • Commonly, the anterior aspect of the hemidiaphragm • Most eventrations are asymptomatic and do not require repair