Biomedical subjects
Publications and source records attributed to M South.
Spontaneous peripheral artery thrombosis in children is rare. We present 2 cases, in both of which the diagnosis was delayed. Acute arterial insufficiency should be considered in children who have clinical symptoms of leg pain, pallor, and reduced pulses. Angiography is the gold standard to confirm or exclude the diagnosis.
The methods of nonbronchoscopic lung lavage used for collection of samples of epithelial lining fluid (ELF) in intubated patients are poorly standardized and incompletely validated. In infants with lung disease requiring ventilatory support, we evaluated two techniques of small volume saline lavage for the collection of a specimen suitable for pulmonary surfactant analysis. We aimed to compare apparent origin of the return fluid obtained by each method, equivalence and agreement of the estimates of measured pulmonary surfactant concentration, and the relative strength of association between surfactant indices and lung dysfunction. Fifty-three contemporaneous paired samples of lung lavage fluid suitable for surfactant analysis were collected from 31 infants using tracheal aspirate (TA, 4 x 0.5 ml saline), and then nonbronchoscopic bronchoalveolar lavage (NB-BAL, 3 x 1 ml/kg). Return fluid from TA had higher mean ELF concentration of total protein and IgA secretory component (SC), and a lower surfactant protein A (SP-A) concentration than NB-BAL, indicating that the TA lavage was sampling ELF more proximally in the tracheobronchial tree (protein: TA 7.7 versus NB-BAL 4.7 mg/ml; SC: 21 versus 1.8 microgram/ml; SP-A: 9.8 versus 19 microgram/ml; all p < 0.01). Mean concentration of surfactant indices in ELF differed only for SP-A, but for all indices, paired values showed poor agreement on Bland-Altman analysis, highlighting the potential imprecision associated with small volume lung lavage. TA return fluid yielded estimates of surfactant indices which were at least equivalent to NB-BAL in prediction of the severity of lung dysfunction. We conclude that NB-BAL return fluid has more distal origin, but analysis of TA fluid may have equal validity in the estimation of indices of pulmonary surfactant. The results of individual estimates of ELF constituents in a single sample of lavage fluid should be interpreted with caution, even when standardized sampling techniques are employed.
Definitive analysis of solute concentrations in lung lavage fluid involves the use of a marker of dilution to correct for variable recovery of epithelial lining fluid (ELF), but the question of the most appropriate dilutional marker remains unresolved. In lavage fluid collected from infants with lung disease and healthy control subjects, we examined ELF concentration of protein, albumin, sphingomyelin (SM), and IgA secretory component (SC), and critically appraised the relative validity of SC and urea as dilutional markers in the context of lung infection and lung injury. Protein, albumin, and SM were found not to be valid dilutional markers, as their ELF concentration varied significantly between the diseased, recovering, and normal lung. Differences in concentration were noted in both tracheal aspirate samples (TA, 4 x 0.5 ml) and nonbronchoscopic bronchoalveolar lavage fluid (NB-BAL, 3 x 1 ml/kg), but were not uniform (e.g., TA-disease versus control: albumin 2.8 versus 0.68 mg/ml, SM 45 versus 16 microgram/ml, both p < 0.05; NB-BAL-disease versus recovery: protein 8.1 versus 4.8 mg/ml, albumin 2.9 versus 1. 4 mg/ml, both p < 0.05). Overall, SC concentrations in ELF were not different between the diseased and normal lung, but in the NB-BAL samples, significantly higher SC concentration was noted in viral bronchiolitis and pneumonia than in noninfective lung diseases. No clear evidence of additional influx of urea into lavage fluid in association with epithelial disruption was found in the diseased lung. Comparative analysis of SC and urea revealed no difference in TA samples, but in NB-BAL specimens, urea best standardized the lavage concentration of surfactant indices to correspond to the degree of lung dysfunction as indicated by oxygenation index. We conclude that SC and urea, but not protein, albumin, or SM, are valid dilutional markers with which to estimate ELF recovery during small volume lung lavage. Urea appears a more appropriate choice in return fluid derived from the distal tracheobronchial tree, and SC should not be used in the context of lung infection.
Traditionally, studies of asthma have concentrated on interventions that were mainly pharmaceutical and outcomes that were usually based on pulmonary function testing. More recently, there has been increasing emphasis on organisational procedures that can enhance the delivery of effective care, and outcomes based more on the clinical than the physiological. Minimum length of stay is targeted as one outcome of benefit for patients and their families. The methods of decreasing hospital stay for asthmatic children which have been proposed and studied are reviewed.
OBJECTIVES: To determine whether children with severe acute asthma treated with large doses of inhaled salbutamol, inhaled ipratropium, and intravenous steroids are conferred any further benefits by the addition of aminophylline given intravenously. STUDY DESIGN: Randomised, double blind, placebo controlled trial of 163 children admitted to hospital with asthma who were unresponsive to nebulised salbutamol. RESULTS: The placebo and treatment groups of children were similar at baseline. The 48 children in the aminophylline group had a greater improvement in spirometry at six hours and a higher oxygen saturation in the first 30 hours. Five subjects in the placebo group were intubated and ventilated after enrollment compared with none in the aminophylline group. CONCLUSIONS: Aminophylline continues to have a place in the management of severe acute asthma in children unresponsive to initial treatment.
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OBJECTIVE: To examine changes to hospital admission rates, length of stay (LOS), bed use, and unplanned readmission rates for children with acute exacerbations of asthma following the change of the Victorian health care system to casemix funding. SETTING: Large university-affiliated children's hospital in Melbourne, Victoria. DESIGN: Prospective collection of data from July 1989 to June 1996 for all children admitted with acute asthma (n = 11939). RESULTS: The number of admissions for acute asthma showed a rising trend before the introduction of casemix funding in July 1993, and subsequently fell. There was a significant fall in mean LOS (64.5 to 39 hours; -40%; P = 0.001), and hence in bed-hours occupied for asthma (115370 to 61116; -47%; P = 0.001). There were no increases in unplanned readmission rates for asthma within the next seven or 14 days. CONCLUSION: LOS and bed use for acute asthma at our hospital have been significantly reduced since the introduction of casemix funding, although this study does not prove a causal relationship. There was no increase in readmission rates, and thus no suggestion of any adverse effects as a result of reducing LOS. The 47% reduction in bed-hours should lead to large reductions in cost to the hospital.
OBJECTIVES: To assess the markers of perfusion which best discriminate survivors from non-survivors of childhood sepsis and to compare the information derived from gastric tonometry with conventionally measured haemodynamic and laboratory parameters. DESIGN: Prospective clinical study of children with sepsis syndrome or septic shock. SETTING: Paediatric intensive care unit in a tertiary referral centre. PATIENTS: 31 children with sepsis syndrome or septic shock. INTERVENTIONS: A tonometer was passed into the stomach via the orogastric route. MEASUREMENTS AND MAIN RESULTS: The following data were recorded at admission, 12, 24 and 48 h: heart rate, mean arterial pressure, arterial pH, base deficit, arterial lactate, gastric intramucosal pH (pHi) and DCO2 (intramucosal carbon dioxide tension minus arterial partial pressure of carbon dioxide). The principal outcome measure was. The secondary outcome measure was the number of organ systems failing at 48 h after admission. There were 10 deaths and 21 survivors. No variable discriminated survival from death at presentation. Blood lactate level was the earliest discriminator of survival. Using univariate logistic regression, lactate discriminated survivors from those who died at 12 and 24 h after admission, but not at 48 h (p = 0.049, 0.044 and 0.062, respectively). The area under the receiver operating characteristic (ROC) curve for lactate was 0.81, 0.88 and 0.89 at 12, 24 and 48 h, respectively. At 12 h after admission, a blood lactate level > 3 mmol/l had a positive predictive value for death of 56% and a lactate level of 3 mmol/l or less had a positive predictive value for survival of 84%. At 24 h a lactate level > 3 mmol/l had a positive predictive value for death of 71% and a level of 3 mmol/l or less had a positive predictive value for survival of 86%. No other variable identified non-survivors from survivors at 12 h. Gastric tonometry could only be done on 19 of the 31 children, of whom 8 died and 11 survived. In these 19 children, DCO2 measured at 24 h, but not at 12 or 48 h, distinguished those who died from those who survived (p = 0.045 and p = 0.20, respectively). The area under the ROC curve for DCO2 measured at 24 h as a predictor of survival was 0.71. Neither the absolute value of pHi nor the trend of change in pHi at any time in the first 48 h identified survivors in this series. The mean arterial pressure distinguished survivors from non-survivors at 24 and 48 h (area under ROC curve = 0.80 and 0.78, respectively). The base deficit and heart rate did not identify non-survivors from survivors at any time in the first 48 h. CONCLUSIONS: Blood lactate level was the earliest predictor of outcome in children with sepsis. In this group of patients, gastric tonometry added little to the clinical information that could be derived more simply by other means.
OBJECTIVES: The purpose of this study was to determine the physiologic variables that predict major adverse events in children in the intensive care unit after cardiac operations. METHODS: A cohort observational study was conducted. At the time of admission to the intensive care unit and 4, 8, 12, and 24 hours later the following variables were recorded: mean arterial pressure, heart rate, cardiac index, oxygen delivery, mixed venous oxygen saturation, base deficit, blood lactate, gastric intramucosal pH, carbon dioxide difference (the difference between arterial carbon dioxide tension and gastric intraluminal carbon dioxide tension), and toe-core temperature gradient. Major adverse events were prospectively identified as cardiac arrest, need for emergency chest opening, development of multiple organ failure, and death. RESULTS: Ninety children were included in the study; 12 had major adverse events and there were 4 deaths. Blood lactate level, mean arterial pressure, and duration of cardiopulmonary bypass were the only significant, independent predictors of major adverse events when measured at the time of admission to the intensive care unit. The odds ratio (95% confidence intervals) for major adverse events if a lactate level was greater than 4.5 mmol/L was 5.1 (1.2 to 21.1), for admission hypotension 2.3 (0.5 to 9.8), and for a cardiopulmonary bypass time greater than 150 minutes 13.7 (3.3 to 57.2). Four hours after admission lactate and carbon dioxide difference, and 8 hours after admission lactate and base deficit, were independently significant predictors. The odds ratios for major adverse events if the blood lactate level was greater than 4 mmol/L at 4 and 8 hours were 8.3 (1.8 to 38.4) and 9.3 (1.9 to 44.3), respectively. At no time in the first 24 hours were cardiac output, oxygen delivery, mixed venous oxygen saturation, toe-core temperature gradient, or heart rate significant predictors of major adverse events. CONCLUSIONS: In the context of our current treatment strategies, the duration of cardiopulmonary bypass and blood lactate level, measured in the early postoperative period, were the best predictors of impending major adverse events.
OBJECTIVE: To test the hypothesis that conventional mechanical ventilation (CV) provides a greater stimulus to secretion of pulmonary surfactant than high frequency oscillatory ventilation (HFO). METHODOLOGY: Sequential examination of surfactant indices in lung lavage fluid in a group of six infants with severe lung disease (group 1), ventilated with HFO and then converted back to CV as their lung disease recovered. A similar group of 10 infants (group 2) ventilated conventionally throughout the course of their illness were studied for comparison. In groups 1 and 2, two sequential tracheal aspirate samples were taken, the first once lung disease was noted to be improving, and the second 48-72 h later. Group 1 infants had converted from HFO to CV during this time. RESULTS: A marked increase in concentration of total surfactant phospholipid (PL) and disaturated phosphatidylcholine (DSPC) was seen in group 1 after transition from HFO to CV; the magnitude of this increase was significantly greater than that sequentially observed in group II (total PL: 9.4-fold increase in group 1 vs 1.8-fold in group 2, P = 0.006; DSPC: group 1 6.4-fold increase vs. group 2 1.7-fold, P = 0.02). CONCLUSION: These findings suggest that intermittent lung inflation during CV produces more secretion of surfactant phospholipid than continuous alveolar distension on HFO, and raise the possibility that conservation and additional maturation of surfactant elements may occur when the injured lung is ventilated with HFO.
AIMS: To determine in children with sepsis syndrome and septic shock the time course of nitric oxide metabolites: nitrate and nitrite (nitrogen oxides). To determine whether serum concentrations of nitrogen oxides distinguished those children who died from sepsis from those who survived; those who required prolonged inotropic support compared with those who did not; and whether there was any relationship of the levels of nitrogen oxides to markers of tissue perfusion. METHODS: Nitrogen oxides were measured in 30 children with sepsis syndrome or septic shock at admission, 12, 24, and 48 hours. A non-septic control group had serum nitrogen oxides measured at admission. Markers of haemodynamics and tissue perfusion measured were mean arterial pressure, blood lactate, base deficit, gastric intramucosal pH, and deltaCO2 (DCO2: the difference between arterial and gastric intraluminal carbon dioxide tensions). Inotrope doses, number of organ systems failing at 48 hours, and outcome as survival were recorded. RESULTS: Children with sepsis had increased nitrogen oxide concentrations at presentation compared with a group of non-septic controls. Children with organ failure at 48 hours had higher serum nitrogen oxide concentrations than those with sepsis uncomplicated by organ failure at 48 hours. There was no difference in nitrogen oxide when patients were subgrouped according to the receipt of inotropes at 48 hours, and no association with markers of tissue perfusion, or survival. CONCLUSIONS: While this study shows that nitric oxide production is increased in sepsis in children, there was a limited relationship with clinically important markers of illness severity and no relationship to survival.
We tested the hypothesis that the composition of bronchial surfactant is normal in infants with cystic fibrosis (CF) in the absence of active lung disease but that it is altered by lower respiratory tract infection and inflammation. We examined the total phospholipid (PL), disaturated phospholipid (DSP), surfactant protein-A (SP-A), surfactant protein B (SP-B), and surface activity in bronchoalveolar lavage fluid from 27 subjects with CF whose mean age was 22.7 (SD 14.5) mo. Six infants with stridor served as non-CF controls. Twelve of the subjects with CF (CF-I group) had evidence of active pulmonary infection or inflammation which was absent in the remaining 15 subjects (CF-NI group). We found no differences in the surfactant composition or activity between controls and the CF-NI group. In contrast, the DSP/PL ratio was lower in the CF-I subjects than in both the CF-NI subjects (p = 0.05) and controls (p < 0.01) suggesting a disturbance of surfactant function. SP-A concentrations were higher in the CF-I group compared to the other two groups (p < 0.05). These results suggest that the bronchial surfactant of infants with CF is altered following lower airway infection and inflammation and is not a primary abnormality associated with this disorder.
The serum concentrations of nitrogen oxides, the stable metabolites of nitric oxide, were measured in 61 children during and after cardiopulmonary bypass (CPB) for surgery of congenital heart disease. Overall, there was a small reduction in serum nitrogen oxide concentrations during CPB, from a median of 27.5 (interquartile range 16.6-55.7) to 26.4 (15.3-40.6) mumol/l, followed by an increase in the following 24 h to 33.1 (21.3-46.7) mumol/l. The largest postoperative increases in nitrogen oxides occurred in children who developed renal impairment, or were treated with nitrovasodilators. There was no relationship between changes in serum nitrogen oxides intraoperatively and early changes in pulmonary vascular resistance, and a weak positive relationship between changes in serum nitrogen oxides and early postoperative changes in cardiac index (r2 = 0.09, p = 0.04). We found no evidence for increased activation of the L-arginine nitric oxide pathway during CPB; and the reduction in nitric oxide metabolites that occurred during CPB were of doubtful significance to pulmonary or systemic haemodynamic changes in the postoperative period.
STUDY OBJECTIVE: To assess the role of gastric tonometry in monitoring children receiving extracorporeal life support (ECLS) and to determine if DCO2 or pHi in the weaning phase of ECLS predicts survival. DESIGN: A prospective study of consecutive patients treated with ECLS. SETTING: A tertiary pediatric ICU that is the ECLS referral center for Australia. PATIENTS: Twenty consecutive children receiving ECLS for cardiovascular or respiratory failure. INTERVENTIONS: All children were monitored throughout their ECLS course using a tonometer inserted into the stomach via the orogastric route. The PCO2 in the tonometer balloon was measured every 4 to 6 h and the pHi was calculated using the Henderson-Hasselbalch equation. The DCO2, which is the difference between PCO2 in tonometer saline solution and arterial blood, was calculated. We compared the ability of pHi, DCO2, heart rate, mean arterial pressure, arterial pH, base deficit, and blood lactate to predict death or survival during the weaning phase. Measurements were taken on the lowest level of support, which for veno-arterial extracorporeal membrane oxygenation and ventricular assist device was defined as the lowest ECLS pump flows, and on veno-venous extracorporeal membrane oxygenation was defined as the time of lowest ECLS gas flow. Predictive power was assessed using the receivor operating characteristic (ROC) analysis on the data collected at these times. RESULTS: In the weaning phase of ECLS, the pHi was significantly lower in children who died (pHi = 7.21; 95% confidence intervals, 7.14 to 7.28) than in those who survived (pHi = 7.38; 95% confidence intervals, 7.28 to 7.47). The DCO2 was significantly higher in children who died (23.6 mm Hg; 95% confidence intervals, 14.3 to 33.1) compared with survivors (4.7 mm Hg; 95% confidence intervals, -0.78 to 10.1). The area under the ROC curve was 0.95 for DCO2 (and 0.88 for pHi). pHi and DCO2 predicted survival better than base deficit (area under ROC curve, 0.82), blood lactate level (0.29), arterial pH (0.65), heart rate (0.62), and mean arterial pressure (0.74). CONCLUSIONS: DCO2 is a clinically meaningful measurement in children receiving ECLS. A high DCO2 was a good predictor of death in this series. Gastric tonometry may provide a useful measure of the adequacy of regional perfusion and oxygenation in this group of patients.
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Preclinical studies have demonstrated that recombinant IFN-alpha (rIFN-alpha) can enhance the tumor associated glycoprotein 72 (TAG-72) on tumors. To determine whether rIFN-alpha could enhance TAG-72 expression in vivo in patients, 15 women with breast cancer were randomized to receive daily injections of rIFN-alpha (3 x 10(6) units/m2 for 14 days) beginning on day 1 (group 1 = 7 patients) or on day 6 (group 2 = 8 patients). On day 3, all patients received a 10-20-mCi tracer dose of 131I-CC49, a high-affinity murine monoclonal antibody reactive against TAG-72, followed by a therapy dose of 60-75 mCi/m2 of 131I-CC49 on day 6. Whole body and single-photon emission computed tomography scans along with whole blood pharmacokinetics were performed following tracer and treatment phases. Hematological toxicity was considerable; reversible grade 3-4 neutropenia and thrombocytopenia was observed in 12 of 15 patients. Twelve of 14 patients tested developed human antimouse antibodies 3-6 weeks after treatment. For group 1 patients, whole blood residence time increased significantly between that predicted from the tracer doses and therapy doses (42.6 +/- 4.7 versus 51.5 +/- 4.8 h, respectively; P < 0.01). The calculated radiation absorbed dose to red marrow from therapy compared to tracer activity was also significantly higher for this group (1.25 +/- 0.35 versus 1. 07 +/- 0.26 cGy/mCi; P < 0.05). Treatment with rIFN-alpha was found to enhance TAG-72 expression in tumors from patients receiving rIFN-alpha (group 1) by 46 +/- 19% (P < 0.05) compared to only 1.3 +/- 0.95% in patients not initially receiving IFN (group 2). The uptake of CC49 in tumors was also significantly increased in rIFN-alpha-treated patients. One partial and two minor tumor responses were seen. In summary, rIFN-alpha treatment altered the pharmacokinetics and tumor uptake of 131I-CC49 in patients at the expense of increased toxicity.
OBJECTIVE: To evaluate inter-observer agreement and validity of an asthma severity score derived from wheeze, heart rate and accessory muscle use components. METHODOLOGY: Children with acute asthma were examined independently and simultaneously by two observers, followed by pulse oximetry and spirometry in those over 5 years with repeatable measurements. RESULTS: Inter-observer agreement was very good (weighted kappa 0.82, 95% confidence interval 0.63 to 1.00), the component with the best agreement being the accessory muscle score (0.76, 0.57 to 0.95). The score correlated significantly with oxygen saturation, heart rate, and forced expiratory volume in 1 s (FEV1). In a multivariate model, FEV1 was best related to accessory muscle use. CONCLUSIONS: The asthma severity score has very good inter-observer agreement with a moderate relationship to oxygenation and FEV1.
To determine whether abnormalities of pulmonary surfactant occur in infants with acute viral bronchiolitis, surfactant indices were measured in lung lavage fluid from 12 infants with severe bronchiolitis and eight infants without lung disease. Compared with controls, the bronchiolitis group showed deficiency of surfactant protein A (1.02 v 14.4 micrograms/ml) and disaturated phosphatidylcholine (35 v 1060 micrograms/ml) which resolved as the disease improved. Surfactant functional activity was also impaired (minimum surface tension 22 v 17 mN/m). These findings indicate that surfactant abnormalities occur in bronchiolitis, and may represent one of the pathophysiological mechanisms causing airway obstruction.