Energy expenditure in children undergoing hematopoietic stem cell transplantation.

Prior studies suggest that patients undergoing hematopoietic stem cell transplantation (HSCT) for malignancy have nutritional needs that are greater than their estimated needs. To determine whether energy estimation equations accurately predict energy expenditure of pediatric patients undergoing HSCT, we prospectively compared the estimated energy expenditure (EEE) and measured energy expenditure (MEE) of 40 patients at four time-points. We also investigated whether energy requirements changed during the transplant period. MEE was determined by indirect calorimetry. Data from 34 patients (autologous HSCT = 10, allogeneic HSCT = 24) were sufficient for analysis. The World Health Organization equation adequately approximated MEE only on day 14 after HSCT. At all other time-points, measured energy expenditure was significantly less than estimated energy expenditure obtained by using the WHO equation (applicable to all patients), the Seashore equation (for patients <15 years of age; n = 19), or the Harris-Benedict equation (for patients > or =15 years of age; n = 15). The median measured energy expenditure varied significantly over the study period and was greatest on day 14 after HSCT. Until accurate equations have been identified for estimating these patients' needs, the use of indirect calorimetry may be medically warranted.

Comparison of energy estimation equations with measured energy expenditure in obese adolescent patients with cancer.

Obesity is increasing in the US adolescent population. As the number of obese adolescents increases, obesity is becoming a more frequent problem in the hospital setting, sometimes causing patients to have complicated and prolonged hospital stays. Calculation of the energy requirements of obese adolescent patients with chronic diseases such as cancer is complicated by increased energy requirements as a result of disease state and growth. This study examined the accuracy of the commonly used equations for calculating energy requirements. Estimated energy expenditure was compared with measured energy expenditure determined by indirect calorimetry. All energy estimation equations were inaccurate, which indicates the need for a specific equation for determination of energy needs in this special patient population. Until further research is done, indirect calorimetry is recommended for all obese adolescent patients with cancer who require nutrition support.

Serial pulmonary function studies in children treated for newly diagnosed Hodgkin's disease with mantle radiotherapy plus cycles of cyclophosphamide, vincristine, and procarbazine alternating with cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine.

BACKGROUND: The pulmonary toxicity of bleomycin-containing chemotherapy combined with mantle radiotherapy in children treated for Hodgkin's disease was longitudinally assessed. METHODS: The results of serial pulmonary function studies in 37 children, newly diagnosed and treated at St. Jude Children's Research Hospital between September 23, 1983, and June 30, 1988, with cyclophosphamide, vincristine, and procarbazine (COP) alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) plus low dose mantle radiotherapy are analyzed. All patients had pulmonary function studies at least before the first bleomycin dose, after completion of radiotherapy, and serially upon discontinuation of therapy. Bleomycin therapy was withheld whenever measured carbon monoxide diffusing capacity was less than 50% of the predicted value. RESULTS: Vital capacity, diffusing capacity, and diffusing capacity per unit of alveolar volume declined during the first 6 months of therapy but improved there after. At 2 years postdiagnosis, diffusing capacity per unit of alveolar volume remained significantly reduced. Only one patient was symptomatic at the 2-year point. The survival rate of these patients was 95% at a median follow up of 93 months. CONCLUSION: If bleomycin is with held when diffusing capacity is diminished to 50% predicted, clinical compromise of pulmonary function appears to be minimal in pediatric patients receiving alternating cycles of COP/ ABVD in combination with low-dose mantle radiotherapy. Survival was excellent, even with reduction of the total bleomycin dose.

Postoperative outcome following thoracotomy in the pediatric oncology patient with diminished pulmonary function.

Surgical resection of pulmonary metastatic disease is often indicated in pediatric malignancies. Although several adult studies document increased postoperative morbidity in adults with diminished pulmonary function, there is little information in the pediatric population or in patients with restrictive lung disease. We reviewed the postoperative course following thoracotomy in patients with diminished pulmonary function (FVC, FEV1, or TLC less than 80% predicted). Thirty-two thoracotomies were performed in 19 patients. The preoperative FVC (% predicted) was 68 +/- 3.6 with a postoperative value of 60 +/- 2.4 (P < 0.01). The preoperative FEV1 was 69 +/- 4.2 with a postoperative value of 60 +/- 3.8 (P < 0.01). Although there was a significant drop in pulmonary function tests (PFTs) following surgery, there was not a significantly greater loss when comparing patients with mild, moderate, and severe disease. When considering postoperative morbidity, there were 3 events (prolonged oxygen requirement, need for postoperative ventilation, or persistent air leak) following 20 surgeries in patients with mild preoperative respiratory dysfunction, 5 events (including one death) in the 7 patients with moderate dysfunction, and 3 events following 5 surgeries in patients with severe dysfunction. There was no correlation with a decrease in any specific PFT and the occurrence of postoperative morbidity. Our limited review suggests that aggressive surgical treatment of metastatic pulmonary disease is tolerated even in patients with severe decreases in pulmonary function.

Efficacy and toxicity of multiagent chemotherapy and low-dose involved-field radiotherapy in children and adolescents with Hodgkin's disease.

PURPOSE: Between May 1980 and September 1990, 85 patients with Hodgkin's disease were treated with a regimen designed to increase cure rates while reducing late toxicity. PATIENTS AND METHODS: Therapy consisted of five cycles of cyclophosphamide, Oncovin (vincristine; Eli Lilly and Co, Indianapolis, IN), and procarbazine (COP), alternated with four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and low-dose (20 Gy) regional radiotherapy. Vincristine and cyclophosphamide were administered as tolerated during irradiation and during the 2- to 4-week rest period between radiation volumes. The need for staging laparotomy was defined by clinical presentation. RESULTS: The median age at diagnosis was 14 years (range, 4 to 20), and 56% of patients were male. The majority (67%) had stage III or IV disease and 68% (19 of 28) of stage II patients had bulky mediastinal disease. Nodular sclerosing histology predominated (67%). Ninety-three percent of patients were alive without disease with a median follow-up of 4.1 years. Abnormalities were detected on chest roentgenograms and/or pulmonary function tests in 58% and 25% of clinically asymptomatic patients who were tested at least 1 year after completion of therapy. The only symptomatic patient had pulmonary fibrosis after treatment with bleomycin (20 U/m2) and mantle (20 Gy)/lung (13 Gy) irradiation, and developed multiple spontaneous pneumothoraces that required cortical stripping. One patient had congestive heart failure 19 months post-treatment, and two had abnormalities on echocardiograms. Thyroid abnormalities occurred in 21 (27%) patients who were assessable for late toxicity. The majority of female patients have had regular menstrual cycles. Six developed ovarian failure, and 10 have had a total of 17 pregnancies. Other than one documented case of oligospermia, information was not available on male fertility. CONCLUSION: The results demonstrate excellent disease control for the COP/ABVD regimen, with acceptable toxicity.

Role of flexible bronchoscopy in the diagnosis of pulmonary infiltrates in pediatric patients with cancer.

We reviewed 60 consecutive flexible bronchoscopies done during a 36-month period in 48 pediatric cancer patients with undiagnosed pulmonary infiltrates. Diagnostic procedures during bronchoscopy included 40 brushings, 50 bronchoalveolar lavages, and 6 transbronchial and mucosal biopsies. A total of 16 specific diagnoses were made by bronchoscopy (27% diagnostic yield), including infection (12), pulmonary leukemia (3), and lymphoma (1). The largest proportion of specific diagnoses came from lavage (14/50) and the smallest from brushings (1/40). Biopsies were also useful for selected patients. The low overall yield for bronchoscopy was probably due to the routine use of empiric broad-spectrum antibiotics and antifungal therapy, as well as trimethoprim-sulfamethoxazole prophylaxis for Pneumocystis carinii pneumonitis. Subsequent specific diagnoses were obtained by other procedures (open biopsy, needle aspiration, or autopsy) for 10 patients with negative bronchoscopy results and 3 patients with diagnostic bronchoscopies. These additional diagnoses included 7 infections (Pneumocystis carinii (1), Candida tropicalis (1), cytomegalovirus (1), and Aspergillus (4), and 6 other diagnoses with nonspecific histologic findings. A positive bronchoscopy result may be useful, but negative bronchoscopy findings do not justify delaying other diagnostic procedures or discontinuing antibiotic and antifungal therapy in children with cancer and pulmonary infiltrates.

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 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.

Effect of methylprednisolone on bacterial clearance and endotoxin liberation during experimental sepsis induced by gram-negative bacteria.

To determine the effect of methylprednisolone administration on the clearance of bacteremia and the release and clearance of endotoxin during antibiotic therapy of gram-negative bacterial sepsis, Escherichia coli K1 sepsis was induced in paired rabbits. Moxalactam and either methylprednisolone or placebo were administered to infected rabbits 1.5 h after intraperitoneal administration of live bacteria. Serial blood samples were obtained for quantitation of bacteremia and endotoxemia, arterial blood gases, and complete blood count. Arterial blood pressure, heart rate, and core body temperature were also monitored. There were no significant differences between the methylprednisolone-treated and placebo-treated groups in either the levels of bacteremia or endotoxemia or in the physiologic, metabolic, or hematologic parameters that were measured. We conclude that methylprednisolone administration has no acute effect on bacterial clearance or on the kinetics of endotoxin release and clearance during antibiotic therapy of gram-negative bacterial sepsis in this experimental model.

Course of pulmonary dysfunction in children surviving Pneumocystis carinii pneumonitis. A prospective study.

Pulmonary function studies were done serially in 23 children 7 to 18 yrs of age who had survived the acute stage of Pneumocystis carinii pneumonitis. Each child was asymptomatic. Spirometric indices, expiratory flows, pulmonary gas transfer factor, arterial blood gases, and other clinical variables were assessed a few days before patients were discharged from the hospital and at 1-, 3-, 6-, and 12-month intervals thereafter; two patients developed recurrent pneumonitis during follow-up and were studied twice. All but five subjects had pulmonary dysfunction when tested initially. A decrease in pulmonary gas transfer factor, observed in 17 studies, was the most common abnormality. Restrictive pulmonary disease was seen in 11 studies; an obstructive component, in one. Arterial hypoxemia at rest, while patients were breathing room air, was noted in nine cases. Roentgenographic evidence of bilateral diffuse lung opacities was seen in 11 patients and was positively correlated with decreases in pulmonary gas transfer factor (p less than 0.001). Arterial hypoxemia was significantly related to intrapulmonary right-to-left shunt (p less than 0.001) but not to decreases in pulmonary gas transfer factor, indicating the importance of ventilation-perfusion abnormalities in these patients. Serial follow-up studies disclosed significant improvement in pulmonary function deficits within 1 month and complete resolution by 6 months in all survivors. Recovery was not related to the amount of duration of O2 therapy, to the need for ventilatory support, or to chest roentgenographic abnormalities. Histopathologic findings in nine patients who died during follow-up did not indicate any residual interstitial fibrosis, collagen deposits, or alveolopathy. We conclude that Pneumocystis carinii pneumonitis during childhood does not typically produce long-lasting pulmonary sequelae.