Faculty Bibliography

OBJECTIVE: To examine the clinical and pathologic features of acute hypoxemic respiratory failure in children. DESIGN: Retrospective review of medical records and pathologic material during a 44-month period. SETTING: Multidisciplinary pediatric ICU. PATIENTS AND METHODS: With the assistance of a computerized database, the medical records of 2,254 pediatric ICU admissions were evaluated to identify children with respiratory failure. Children with acute hypoxemic respiratory failure who met the following definition were selected for inclusion: a) PaO2 less than 75 torr (less than 10.0 kPa) with an FIO2 of greater than 0.5; b) diffuse bilateral infiltrates on chest radiograph; and c) exclusion of cardiogenic pulmonary edema clinically or by pulmonary artery catheterization. Patients were excluded if they did not receive tracheal intubation and assisted ventilation. The medical records were reviewed for demographic, clinical, and physiologic information. Pathologic findings from autopsy or lung biopsy were also reviewed. Patients were placed in one of six groups based on their underlying disorder. In addition, the presence of neutropenia, septic shock, or a history of bone marrow transplantation was noted as a coexisting condition. MAIN RESULTS: A total of 100 acute hypoxemic respiratory failure patients were identified (4.4% of all 2,254 pediatric ICU admissions; 50 male, 50 female). Mean age was 6.0 +/- 5.4 (SD) yrs (range 1 month to 18 yrs). The overall mortality rate was 72%. The mortality rate was not affected by the underlying disorder, but it was higher in the presence of septic shock (80% vs. 58%; odds ratio 2.8), neutropenia (88% vs. 64%; odds ratio 4.0), and bone marrow transplantation (95% vs. 66%; odds ratio 10.4). When multivariate regression analysis was performed using all coexisting conditions, human immunodeficiency virus status, and patient gender, only a history of bone marrow transplantation and gender appeared to affect outcome. Oxygenation ratio (PaO2/FIO2), alveolar-arterial oxygen tension difference, duration of exposure to high levels of oxygen, and airway pressure measurements indicated more severe derangement of pulmonary function in those patients who died. Cardiac function was similar in survivors and nonsurvivors. Respiratory failure occurred in 32 children with severe neutropenia (mean absolute neutrophil count 55 +/- 101 cells/mm3), including 16 children with an absolute neutrophil count of 0. Pulmonary tissue from 37 children was studied. Diffuse alveolar damage was observed in 24%; morphologic evidence of infectious pneumonitis was encountered in an additional 41%. CONCLUSIONS: Children with acute hypoxemic respiratory failure represent a heterogeneous subset of patients. In our group of patients, infectious pneumonitis was more commonly encountered than diffuse alveolar damage. The mortality rate of children with acute hypoxemic respiratory failure has not improved since 1980.

In a retrospective study we assessed the hepatic changes in children with the acquired immunodeficiency syndrome by reviewing 12 biopsy specimens and 48 autopsy specimens from 54 children. Hepatopathology differed in biopsy and autopsy material. In biopsy specimens, chronic active hepatitis with predominantly T8 lymphocytes by tissue immunochemistry was common (five of 12 specimens). Fatty degeneration and hepatocellular necrosis were either absent, mild, or patchy. On the other hand, at autopsy, chronic active hepatitis was not observed. The most prominent changes were extensive fatty degeneration, nonspecific portal mononuclear infiltration, portal fibrosis, and confluent (ischemic) necrosis. Opportunistic infections such as Mycobacterium avium-intracellulare (MAI) were noted only at autopsy. In addition, three unusual morphologic characteristics were noted: nodular lymphoplasmacytic portal infiltrate, a pseudosarcomatous variant of Mycobacterium avium-intracellulare infection, and multinucleated giant cells (foreign both type and giant cell transformation of hepatocytes).

A cyanotic, tachypneic newborn was diagnosed to have double-outlet right ventricle of the Taussig-Bing type. Cardiac failure did not respond to medical treatment or surgical palliation. Postmortem examination revealed two ventricular septal defects (VSDs), one a malalignment VSD in the membranous septum and adjacent tissue and the other in the anterosuperior part of the muscular septum. The D-malposed aortic root emerged mainly from the right ventricle, with aortic-mitral continuity. The larger posterolateral pulmonary root arose almost entirely from the right ventricle, confluent with the muscular VSD, and unrelated to the mitral valve. Its right ventricular aspect was obstructed by hypertrophied infundibulum. This unique malformation of the heart functioned as a double-outlet right ventricle of Taussig-Bing type. In addition, however, the malformation had elements of tetralogy of Fallot because of the malaligned VSD and hypertrophied conal musculature (although pulmonary flow was excessive), and also of complete transposition of the great arteries because of the arrangements of the two VSDs, which favored aortic flow from right ventricle and pulmonary blood flow from the left ventricle. Thus, a single heart presented similarities to three anatomic and functional entities.

In four neonates with perinatally lethal osteogenesis imperfecta (OI) who survived for more than 9 days after birth, vascular congestion and acute hemorrhage were found in 10 of 11 parathyroid glands; in one neonate, all four parathyroid glands, including the only gland without acute hemorrhage, contained abundant deposits of stainable iron. One neonate had hypocalcemia, and one had both hyperphosphatemia and hypocalcemia. In four neonates with OI who died within 72 minutes of birth, all 10 parathyroid glands demonstrated were free of hemorrhage and hemosiderin deposition. Only minor foci of acute hemorrhage were seen in three of 170 glands in 113 comparison neonates and infants. We conclude that parathyroid gland hemorrhage is common in perinatally lethal OI with survival beyond the immediate period of birth, and is otherwise rare. We speculate that parathyroid hemorrhage may be related to difficulty in maintaining postnatal calcium homeostasis in the absence of adequate calcium reserves in bone. Acute parathyroid gland hemorrhage causes fluctuations in serum calcium levels that have on occasion proved fatal, and parathyroid hemorrhage may be a proximate cause of death in some neonates with OI.

Intrauterine infection with parvovirus B19 may lead to fatal hydrops fetalis. Intranuclear particles, consistent with parvovirus virions, within erythroid cells were readily identified on transmission electron microscopy of formalin-preserved material obtained at necropsy from a neonate and two fetuses in whom clinical and light microscopic criteria for parvovirus B19 infection were met. No such particles were seen in similar material from a neonate and two fetuses with erythroblastosis fetalis due to alpha-thalassemia, maternofetal Rh incompatibility, and an erythrocyte membrane protein defect. When other means of investigation are impracticable transmission electron microscopy is widely available and easily performed and may be of value in establishing a diagnosis of parvovirus B19 infection.