A prospective study of Hickman/Broviac catheters and implantable ports in pediatric oncology patients.

We prospectively studied the continuous function and complication rates of 286 central venous catheters consecutively placed in 264 children and young adults at a single institution over a 19-month period (median follow-up, 376 days). Externalized catheters (91 Hickman [H], 113 Broviac [B]) and implantable ports (n = 82) were compared for complications, including infection and thrombosis. The most frequent major complication of all catheters was infection, although the rates of infection varied with the duration of catheter use and were generally lower than reported by others. Overall, when catheter failures (removal) for infection, obstruction, or dislodgement were considered, ports had a significantly longer failure-free duration of use (P = .0024) than did externalized catheters. Likewise, ports had a significantly longer infection-free (P less than .01) duration of use than H and B catheters. However, differences in patient age and clinical characteristics among the three catheter groups may have affected the outcome. In analysis of pairs matched for diagnosis, therapy, and age, ports had lower infection rates than did B catheters after 100 days (P = .053). This difference became significant at 400 days of catheter use (P = .029). Although there was a trend toward lower rates of infections for ports v H catheters, this difference was not significant. In view of our results in matched pairs, selection of catheter type based on clinical characteristics and patient preferences remains a reasonable therapeutic approach despite the apparent advantages of ports. The superiority of ports for long-term use (greater than 100 days) needs to be confirmed in a large randomized clinical trial.

Presentation of Pneumocystis carinii pneumonia as unilateral hyperlucent lung.

Pneumocystis carinii pneumonia (PCP) presented as unilateral hyperlucent lung in a 27-month-old patient with a brain tumor who was receiving chemotherapy. Although unilateral pneumonia is an uncommon presentation of PCP in non-AIDS patients, PCP must be suspected in any pediatric cancer patient not receiving trimethoprim-sulfamethoxazole prophylaxis and receiving intensive chemotherapy.

Spirometry and chest wall dimensions in achondroplasia.

Standard values for pulmonary function in short-limbed dwarfism are not available. Therefore, chest diameters and expiratory spirograms were measured in 58 female and 44 male subjects between 7 and 60 years of age with achondroplasia, the most common form of dwarfism. Standing height in adults was 49.6 +/- 3.2 (SD) inches with a sitting/standing height ratio of 0.66 (normal 0.52-0.53). Despite extremely short stature, only AP chest diameters in males were smaller than control subjects of similar age. The following equations were derived for forced vital capacity (FVC): males (under 25 years), FVC(L) = -3.56 + 0.162 X sitting height (in) + 0.067 X age (yrs); males (over 25 years), FVC(L) = -0.73 + 0.162 X sitting height (in) -0.047 X age (yrs); females (under 20 years), FVC(L) = -3.56 + 0.150 X sitting height (in) + 0.067 X age (yrs); females (over 20 years), FVC(L) = -1.92 + 0.150 X sitting height (in) -0.016 X age (years). Similar prediction equations were derived for FEV1 and FEF25-75%: FEV1/FVC % was 84.2 (+/- 6.5) for females and 88.0 (+/- 6.5) for males. We also compared the observed FVC measurements to values calculated using standing heights derived from the subject's sitting height, assuming a normal body proportion. The observed vital capacity in achondroplasia was only 67.6 (+/- 19.2) percent of that predicted for normally proportioned females and 72.4 (+/- 13.6) percent for males, suggesting reduced vital capacity in achondroplasia, due to reduced chest wall compliance or abnormal lung growth.

Postural hypoxemia in cystic fibrosis.

We measured arterial blood gases in the sitting and supine position in 33 patients with cystic fibrosis (CF). Arterial PO2 ranged from 48 to 97 mm Hg in the sitting position and fell by 1 to 23 mm Hg in 26 patients, rose by 1 to 4 mm Hg in five, and was unchanged in two when supine. Mean PO2 change for the group was a 6.5 (+/- 6.8) mm Hg decrease (sitting to supine), and substantial falls were more likely to occur in patients with mild to moderate, rather than severe, obstructive lung disease. There were no significant changes in PCO2 or pH with posture. Postural hypoxemia was not completely explained by greater airway closure as measured by the single-breath nitrogen method in 11 patients or by worse radiographic change in the upper lung zones. Arterial PO2 should always be compared in the same body position in CF patients, preferably while supine. Postural hypoxemia also may contribute to the lower PO2 at night in CF patients.

The lungs and airways in achondroplasia. Do little people have little lungs?

Achondroplasia is a unique model of the effects of skeletal dysplasia and dwarfism on the respiratory system. We measured chest dimensions, spirometry, lung volumes, maximal expiratory flow volume curves, nasal and airways resistance, closing volume, maximal inspiratory/expiratory pressures, and tracheal area by acoustic reflection in 12 healthy subjects with achondroplasia. Anterior-posterior thoracic diameter was mildly reduced in men. Vital capacity for all subjects was 108 percent +/- 18.6 percent (SD) of that predicted for achondroplastic subjects, but was reduced when compared with values for people of average stature that were predicted, based on either sitting height or thoracic height. The reduction was relatively greater in male than in female subjects. The RV/TLC and FRC/TLC ratios were normal. Other measurements were similar to those in average-statured adults. We conclude that achondroplasia results in a reduction in vital capacity out of proportion to what would be expected if these subjects had normal limb size. Although the lungs may be small, they are functionally normal, as are the airways.

Use of oral contraceptives in women with cystic fibrosis.

Oral contraceptive pills (OCP) represent the most common contraceptive method among teenagers and young adults. Because many women with cystic fibrosis (CF) are now surviving into childbearing age and are at risk for the complications of pregnancy in CF, oral contraceptive use may be indicated. However, it has been suggested that OCP use by CF patients may be associated with deterioration in pulmonary function. Ten adolescent and young adult women with CF and moderate-to-severe obstructive lung disease were studied while taking a combination oral contraceptive pill (Ovral 28). No significant deterioration was found in clinical status or pulmonary function. Careful follow-up should nevertheless be continued to monitor for other adverse effects of oral contraceptive use in CF, such as cholelithiasis.

In situ management of confirmed central venous catheter-related bacteremia.

Thirty-one patients with suspected central venous catheter-related bacteremia were evaluated with comparative quantitative cultures of central venous and peripheral blood specimens. Using criteria developed from studies in bacteremic animals, 19 patients were confirmed to have catheter-related bacteremia. Antibiotic therapy was administered through the catheter (in situ therapy) in 17 of those patients to evaluate the feasibility of treating patients with true central venous catheter-related bacteremias without catheter removal. Bacteremia was successfully eradicated in 11 of 17 patients (65%), allowing 7 patients to retain their catheter a median of 157 days. This study validates the use of comparative quantitative blood cultures in the diagnosis of catheter-related bacteremia and indicates that in situ therapy is a rational alternative to catheter removal in patients with catheter-related bacteremia.

Effects of corticosteroids on postnatal lung and airway growth in the ferret.

To investigate the influence of corticosteroids on postnatal lung and airway growth, young male ferrets were given cortisone acetate (20 mg/kg im daily) beginning at 8 wk of age. At 19 wk of age pulmonary function was measured. The lungs were excised for measurements of recoil pressures and wet and dry weights. The dimensions of central and peripheral airways were estimated from analysis of bronchial casts. Corticosteroid-treated animals were shorter and tended to be lighter than control animals but were heavier in relation to length. Total lung capacity was reduced in proportion to the reduction in body size. Lung recoil and wet-to-dry weight ratios were nearly identical. Maximal expiratory flows were reduced in proportion to the reduction in body size. Size-corrected airway conductance was reduced, suggesting a sensitivity of central airways to growth suppression by corticosteroids. Peripheral airways, on the other hand, were not smaller in treated animals and were larger in proportion to body size. In the ferret corticosteroid administration is associated with a suppression of lung parenchymal growth similar to that of overall body growth. The peripheral airways may be less sensitive and the central airways more sensitive to the effect of corticosteroids on growth.

Pulmonary function following varicella-zoster pneumonia in children with leukemia.

Varicella-zoster virus (VZV) is a cause of serious pneumonias in immunosuppressed patients. Although there are reports of residual lung changes in adults following VZV pneumonia, no previous studies of lung function in children following this infection have been done. We studied 11 patients (median age 11 years) who had had VZV pneumonia 1 to 16 years previously. All patients had a primary diagnosis of acute lymphocytic leukemia. Pneumonia was mild in most of the patients: Three had only radiographic evidence of pneumonia and required no supplemental oxygen, and seven required an FiO2 less than or equal to 0.4 for intervals for up to 11 days. One patient had severe pneumonia and required major ventilatory support. Three patients (27%) had significant restrictive defects on follow-up, with total lung capacity 62-69% predicted; and a fourth was abnormal at 1 month follow-up but normal at 16 months. No obstructive defects were noted, although RV/TLC ratios were elevated in three patients and volume of isoflow increased in three. Single breath diffusing capacity was reduced in two patients, but gas exchange was normal in all. No residual radiographic changes were present except in the patient who had severe pneumonia and increased lung markings at 2 months follow-up. All three patients with restrictive changes had other infections before or following VZV, including Pneumocystis carinii pneumonia in two and recurrent, nonspecific pneumonias in the third. We conclude that VZV pneumonia had minimal residual effects on lung function in children with leukemia.

Bronchoscopic airway evaluation facilitated by the laryngeal mask airway in pediatric patients.

The laryngeal mask airway (LMA) was introduced for clinical use in 1988. It represents a new concept in airway management. Its role has been described as filling the gap between tracheal intubation and the anesthesia face mask. It is inserted without direct visualization into the hypopharynx and when properly positioned forms a low pressure seal around the laryngeal inlet, allowing spontaneous as well as gentle positive pressure ventilation. Since its introduction, its indications and applications in anesthesia practice have increased. Although initially used as a means of delivering anesthesia and obviating the need for holding a mask on the patient, its position directly over the laryngeal inlet makes it a useful guide during flexible bronchoscopy. We report our experience in six pediatric patients and describe an anesthetic technique for bronchoscopy using the LMA for general anesthesia with spontaneous ventilation.

Epidemiologic study of cystic fibrosis: design and implementation of a prospective, multicenter, observational study of patients with cystic fibrosis in the U.S. and Canada.

Cystic fibrosis (CF) is a complex illness characterized by chronic lung infection leading to deterioration in function and respiratory failure in over 85% of patients. An understanding of the risk factors for that progression and the interaction of these factors with current therapeutic strategies should materially improve the prevention of this progressive lung disease. The Epidemiologic Study of Cystic Fibrosis (ESCF) was therefore designed as a multicenter, longitudinal, observational study to prospectively collect detailed clinical, therapeutic, microbiologic, and lung function data from a large number of CF treatment sites in the U.S. and Canada. The ESCF also serves an important role as a phase-IV study of dornase alfa. To be eligible for enrollment, subjects must have the diagnosis of CF and receive the majority of their care at an ESCF site. In this paper, the authors present the ESCF study design in detail. Further, enrollment data collected at 194 study sites in 18,411 subjects enrolled from December 1, 1993 to December 31, 1995 are presented in summary form. This comprehensive study is unique in the detail of clinical data collected regarding patient monitoring and therapeutic practices in CF care. Two companion articles present data regarding practice patterns in cystic fibrosis care, including data on resource utilization and prescribing practices.

Early detection and simplified management of obstructed Hickman and Broviac catheters.

Thrombotic occlusion of Hickman and Broviac central venous catheters is a serious obstacle to their long-term use. Because resistance to flow (R) through a catheter of lumen radius, r, is proportional to 1/r4, we hypothesized that measurement of R would provide an objective and sensitive monitor for partial occlusions. Our measurements showed that median R at a flow of 17 mL/min was 0.7 cmH2O/mL/min in normally functioning Hickman catheters, and 4.1 cmH2O/mL/min in Broviac catheters. In obstructed catheters, which by subjective standards resisted flushing or blood withdrawal, median R was 3.0 cmH2O/mL/min for Hickman and 5.6 cmH2O/mL/min for Broviac catheters, representing significant increases. In a series of obstructed lines in which urokinase was administered, R decreased from 7.7 to 4.5 in Hickman catheters and from 5.6 to 4.2 in obstructed Broviac catheters. The elevated resistance in Hickman catheters after urokinase suggested that residual catheter obstruction was present even though catheter function returned to normal. Elevated R was seen with abnormal venograms in seven of 13 patients. Four patients had normal R values and abnormal venograms, and two patients had elevated R values with normal venograms. Measurement of resistance in Hickman and Broviac catheters provides a simple technique that can supplement or replace venography in the serial assessment and treatment of partial obstruction.

Pulmonary complications of tissue transplantation in children.

Pediatric bone marrow transplantation and transplantation of solid organs rapidly expanded during the 1980s. Antibiotic therapy for bacterial pneumonias, improved transplant preparative regimens, and improvements in prevention and therapy of graft-versus-host disease have made possible significant improvements in overall bone marrow transplant survival. Despite these advances, pulmonary complications of transplantation remain major causes of morbidity and mortality in pediatric transplant patients. Fungal and cytomegalovirus infections have emerged as the major posttransplant pulmonary infections whereas idiopathic interstitial pneumonias and bronchiolitis obliterans are the major noninfectious pulmonary problems. Recent developments in antiviral therapy for cytomegalovirus pneumonia offer hope that the dismal prognosis of cytomegalovirus pneumonia in transplant patients can be improved. New early detection methods for cytomegalovirus using polymerase chain reaction may also help identify patients for prophylactic therapy and prevent development of cytomegalovirus pneumonitis. Early diagnosis and treatment for fungal pneumonias and other opportunistic pathogens remain significant challenges in immunocompromised transplant patients.

Varicella zoster and herpes simplex virus pneumonias.

Varicella zoster (VZV) and herpes simplex (HSV) viruses commonly cause self-limited infection of the skin and mucous membranes. However, certain groups of subjects, including neonates, cancer patients, organ and bone marrow transplant recipients and those with congenital or acquired deficiencies of cell mediated immunity, are at increased risk for dissemination of either virus to the lungs and/or other viscera. The highest risk for VZV pneumonitis is in bone marrow transplant recipients, 44%, and in children with acute leukemia, 32%. The mortality from this complication of VZV infection in the preantiviral era was at least 25%. Except for neonates, dissemination and mortality rates for HSV infections are less than for VZV infections in the high risk groups. Cell-mediated immunity has a major role in both recovery from primary infection and modulation of latent infection, but antiherpes antibodies also have an important role in moderating the extent and severity of infection. Both viruses cause a patchy nodular pneumonia with scattered necrotic and hemorrhagic foci. Physical examination is often misleading and rapid progression of pneumonia can occur within hours. Intravenous acyclovir, administered early in the course of HSV and VZV infection at dosages of 250 mg/m2 and 500 mg/m2 every eight hours, respectively, has nearly eliminated the risk of severe symptomatic pneumonitis. Treatment of established pneumonitis with acyclovir at these doses has also reduced the mortality of herpesvirus pneumonias.

Cryptosporidiosis in ferrets.

The diagnosis of cryptosporidiosis in two ferrets who died from unrelated causes prompted a survey to determine the prevalence and incidence of the infection in ferrets at our facility. The survey of the existing ferret population and all new arrivals indicated cryptosporidiosis occurred as a subclinical disease in a high percentage of young ferrets: 40% of the ferret population and 38 to 100% of the new arrivals had cryptosporidial oocysts in their feces. The infection was found to persist for several weeks in both immunocompetent and immunosuppressed ferrets. The interspecies transmission of Cryptosporidium implies that infected ferrets should be considered a potential source of infection for the general population.

Lack of antibacterial activity after intravenous hydrogen peroxide infusion in experimental Escherichia coli sepsis.

The intravenous administration of hydrogen peroxide has been reported to benefit patients with pneumonia and to reduce Plasmodium parasitemia in experimentally infected mice. We assessed the antibacterial activity of intravenously infused hydrogen peroxide against hydrogen peroxide-susceptible Escherichia coli (MBC of hydrogen peroxide, 0.23 mM) in experimentally infected rabbits. No decrease in the level of bacteremia was detected at the maximum intravenous infusion rate of hydrogen peroxide physiologically tolerated by the rabbits (2.0 mumol/h). Moreover, the addition ex vivo of greater amounts of hydrogen peroxide to human or murine blood containing E. coli resulted in no detectable antibacterial action. In contrast, ethyl hydrogen peroxide, which is not affected by catalase, was bactericidal when added ex vivo to human blood containing E. coli. These results suggest that extracellular hydrogen peroxide, whether of exogenous or endogenous origin, does not have antibacterial activity in the blood of animals having even low levels of catalase.

Postsepsis bradycardia in children with leukemia.

OBJECTIVE: We observed sinus bradycardia in a small number of children with hematologic malignancies who were recovering from sepsis. Our objective was to define this symptom complex and attempt to delineate its etiology. DESIGN: Retrospective chart review. SETTING: A pediatric ICU in a children's oncology hospital. PATIENTS: Children admitted to the ICU over a 24-month period who developed persistent bradycardia (heart rate less than 5% for age for greater than 1 hr) after an episode of sepsis. MEASUREMENTS AND MAIN RESULTS: Seven children developed postsepsis bradycardia. Six patients had a primary diagnosis of acute myelogenous leukemia and one patient had acute lymphocytic leukemia. All patients had positive blood cultures (Streptococcus mitis, n = 4; Escherichia coli, n = 2; and Klebsiella pneumoniae, n = 1). All seven children were clinically recovering from sepsis when the bradycardia developed. Neither hypotension nor other symptom was associated with the bradycardia. No therapy was given for the bradycardia. Echocardiograms and ECGs were normal in all patients, except for the presence of bradycardia. Bradycardia persisted for 24 to 72 hrs. After that time, heart rates slowly increased to the normal range for age. CONCLUSIONS: We speculate that this syndrome may result from alterations in beta-adrenergic receptor function or an unidentified humoral factor produced by the invading organism or as part of the host's response to sepsis. Prior drug therapy or the underlying illness may predispose to this condition, since all the patients had acute leukemia. As the bradycardia was clinically insignificant, invasive therapeutic or diagnostic strategies were not indicated.

Fetal alcohol syndrome: seven new cases.

In one year, the "fetal alcohol syndrome" (FAS) was recognized in seven newborn and older infants, bringing the total in the current literature to 26 cases. This recently rediscovered disorder consists of severe prenatal and postnatal growth failure, mental deficiency, and characteristic hypoplasia of the middle face and orbits with minor malformations of the heart and joints. The mothers have chronic alcoholism. By identifying and counseling such women, obstetricians and gynecologists may prevent the occurrence of the syndrome or diagnose it in the neonate.

Transbronchial lung biopsy in pediatric and adolescent patients.

Since data are unavailable on the role of transbronchial lung biopsy (TBB) in pediatric and adolescent patients, we reviewed our two-year experience in 12 patients (median age, 14.5 years). In all 12, the indication for TBB was a persistently abnormal chest roentgenogram (nine with multilobar infiltrates, two with unilateral infiltrates, and one with a cavitary lesion). Overall, a specific diagnosis was made by TBB in six patients, including three patients with sarcoidosis, one with lymphoma, and two with eosinophilic granuloma. In three additional patients, nonspecific histologic findings on TBB combined with clinical findings, roentgenographic patterns, and supplemental laboratory data helped support a diagnosis. Although the need for general anesthesia and the small size of the biopsy specimens may limit the usefulness of TBB in most pediatric patients, TBB may be a useful alternative in carefully selected patients.