Composition of peripheral blood progenitor cell components collected from healthy donors

OBJECTIVES: The purpose of this study was to test the hypothesis that low circulating thyroxine concentrations characteristic of very low birth weight (VLBW) neonates (< 1500 g) are the result of decreased protein binding of thyroid hormones and to elucidate the mechanism(s) responsible and possible significance thereof. DESIGN: Cross-sectional comparison of thyroid related measurements in cord blood specimens from VLBW infants and from full term infants. Longitudinal comparison in cord and 2- and 4-week blood specimens from VLBW infants. PATIENTS: Cord blood specimens were analysed from 47 VLBW and 45 full term infants weighing > or = 2500 g. Repeat analyses in venous bloods from 32 of the VLBW infants were analysed at 2 weeks of age and again at 4 weeks in 23. The first cohort of patients was studied in 1994 and comprised 28 VLBW and 24 full term infants (Cohort A). The studies were repeated in 1995-96 in 19 VLBW infants and 21 full term infants (Cohort B). MEASUREMENTS: T4, free T4 (FT4), T3, thyroxine binding globulin (TBG), and TSH were measured in cord blood and 2- and 4-week venous specimens from VLBW infants and in cord blood specimens of full term infants. Molar ratios of T4/TBG were calculated. RESULTS: (1) Cord blood TBG, T4 and T3 concentrations of VLBW infants were each 60% of those of term infants. TBG concentrations were 397 +/- 111 vs 680 +/- 172 nmol/l (P < 0.0005). T4 concentrations were 76 +/- 22 vs 139 +/- 26 nmol/l (P < 0.0005). FT4 concentrations were in the normal adult range in both neonatal groups. T4/TBG ratios did not differ between the neonatal groups but were significantly less than that of adults (P < 0.001). (2) TSH concentrations in VLBW infants at 2 and 4 weeks were less than 50% of cord blood values. At 2 weeks, TBG concentrations of VLBW infants were unchanged from cord blood concentrations but mean T4 concentration fell by 18% and T4/TBG ratios by 21% (P < 0.005). Mean FT4 rose by 78% (P < 0.02). The changes in mean T4 and FT4 were due largely to FT4 concentrations of 37-113 pmol/l and T4 concentrations of 13-48 nmol/l in 5 infants. These infants also had lower T4/TBG ratios and were smaller and more ill than the remainder of the cohort. The changes disappeared by 4 weeks in 3 of the 4 infants tested. CONCLUSIONS: Cord T4/TBG ratios are the same in very low birth weight and term infants and are significantly lower than in adult blood. These are more than compensated for in term infants by a 236% increase in thyroxine binding globulin concentrations. The lower thyroxine binding globulin concentrations in very low birth weight infants explain their much lower T4 concentrations. Cord FT4 concentrations of full term and very low birth weight infants are in the normal adult range. T4 concentrations are further depressed and free T4 concentrations elevated in the most ill very low birth weight infants at 2 weeks of age in a manner analogous to that of the 'sick euthyroid syndrome'.     

Ureaplasma urealyticum and chronic lung disease in very low birth weight infants during the exogenous surfactant era

BACKGROUND: An association between recovery of Ureaplasma urealyticum from the respiratory tract of very low birth weight (VLBW) infants (< or =1500 g) and later chronic lung disease (CLD) was reported by several authors before the routine use of exogenous surfactant (SURF). We sought to assess whether this relation persists in the era of routine SURF. METHODS: We prospectively studied a cohort of 105 VLBW infants who required mechanical ventilation at < 12 h of age. Tracheal aspirates for U. urealyticum culture were obtained before administration of SURF or antibiotics. Clinicians were unaware of U. urealyticum status. Chest radiographs at 28 days were reviewed by a single pediatric radiologist, blinded to U. urealyticum status. Sample size was predetermined to detect a 30% increase in CLD among those with U. urealyticum recovery from tracheal culture (U. urealyticum-positive) with alpha <0.05 and beta <0.20. RESULTS: Of the study infants 22 were U. urealyticum-positive and 83 were U. urealyticum-negative. No differences were found between the groups for birth weight, gestational age, gender, inborn, antenatal or postnatal steroid use, SURF therapy, non-U. urealyticum infection, necrotizing enterocolitis, patent ductus arteriosus, intraventricular hemorrhage or cystic periventricular leukomalacia. At 28 days U. urealyticum-positive patients were significantly more likely to have CLD than U. urealyticum-negative [15 of 22 (68%) vs. 30 of 83 (36%); P < 0.02]. The U. urealyticum-positive patients also required significantly longer courses of supplemental oxygen and mechanical ventilation. No significant differences were found for CLD at 36 weeks postconception or duration of hospitalization, although type II error could not be excluded for these secondary endpoints. CONCLUSIONS: Respiratory U. urealyticum at or shortly after birth remains associated with CLD at 28 days despite routine use of SURF. Controlled trials of anti-Ureaplasma therapy in U. urealyticum-positive VLBWs as soon after birth as possible may determine whether CLD, duration of respiratory support and attendant costs can be decreased.     

Feasibility for evaluation of the efficacy of conventional ventilatory support in very low birth weight infants

Morbidity and mortality analysis in prematurely born low birth weight (LBW) neonates, very low birth weight (VLBW) neonates and extremely low birth weight (ELBW) neonates forms the cornerstone in current pediatric decision-making from both medical and socioeconomic point of view. The successful introduction of artificial ventilation for neonatal respiratory failure treatment has changed tremendously the prognosis of many diseases with a fatal outcome. This retrospective observational longitudinal study was designed to evaluate the changes in the following main indices: mean airway pressure (MAP), oxygenation index (OI), arterial-to-alveolar oxygen tension ratio (a/A PO2), alveolar-arterial oxygen gradient (A-a)DO2, ventilation index and VEI in VLBW infants treated with conventional ventilatory support (CV), assess the information yield of these indices as indicators of gas exchange at each and every one moment of CV, and to analyze their feasibility, accuracy and real-time convenience as indicators of the adequacy of inhalation therapy and their role as an indispensable tool in constructing the optimal treatment regimen in VLBW infants. Forty-seven VLBW infants requiring ventilatory support within 24 hours of birth were enrolled in the study. Four of the infants survived and the remaining 43 died. The data collected were entered into a high-yield Neonatal Intensive Computer File and the indices were followed up sequentially and thoroughly analyzed as the primary outcome measures of the study. Our results show that: 1. The combination of indices we propose is a useful high-yield discriminating method for evaluating the efficacy of neonatal ventilatory support, arterial blood gas exchange and clinical status. 2. These indices allow early diagnosis of the changes in pulmonary mechanics, hemodynamics and blood saturation. 3. Using the combination of indices improves the diagnostic reliability and information yield of each one of them. 4. The twofold pattern of change of the indices in VLBW infants is well-recognized:--whereas a/A and OI change rapidly in the group of non-survivors reflecting the delicate balance in optimal gas-exchange using conventional methods in the survivors group there is a sustained tendency towards an increase in a/A values with a concomitant decrease in OI values. The airway pressure is constant in the presence of great fluctuations in OI values reflecting the breakdown in oxygenation at the high price paid for its sustenance in the nonsurvivors group whereas the mean airway pressure showed a gradual decrease in the survivors group and allowed early weaning from mechanical ventilation. (A-a)DO2 remained high in the non-survivors group thus reflecting a high-degree, practically constant shunting whereas the same index showed a tendency towards decrease in the survivors group. 5. These indices allow optimal management of neonatal ventilation and oxygenation and timely correction or a change of the ventilatory or/and oxygenation strategy. 6. This information forms the basis for prognostic conclusions regarding the current status or the survival of the neonates.     

Respiratory drive and pulmonary mechanics during haemodialysis with ultrafiltration in ventilated patients

The improvements of respiratory drive and pulmonary mechanics which follow haemodialysis with ultrafiltration in mechanically ventilated renal failure patients seem predictable but have not been studied before. In this study, 14 renal failure patients with stable haemodynamics mechanically ventilated with pressure support ventilation (PSV) were enrolled. Respiratory drive (represented as P0.1), pulmonary mechanics, breathing pattern, arterial blood gas and haemodynamics were measured according to the time schedule: pre-dialysis (Time 0), and at 60, 120, 180, 240 minutes thereafter. Following the removal of excess lung water during haemodialysis, auto-PEEP and patient's work of breathing (WOBp) decreased gradually. P0.1 lessened progressively along with the improvement in pulmonary mechanics. The changes in auto-PEEP and WOBp correlated closely to the pre- and post-dialysis decline of P0.1 (delta P0.1). There was a negative, moderately significant correlation between the amount of fluid ultrafiltrated during dialysis (delta UF) and the delta P0.1 (R = -0.54). The breathing pattern remained stable during dialysis. No hypoventilation or hypoxaemia occurred despite the development of metabolic alkalosis induced by bicarbonate dialysate. We have shown that respiratory drive decreases gradually during bicarbonate haemodialysis. The improvements of pulmonary mechanics, rather than the rapid alkalization of body fluids, responds to the decrease of P0.1 in renal failure patients ventilated with PSV.     

Impact of erythromycin on respiratory colonization of Ureaplasma urealyticum and the development of chronic lung disease in extremely low birth weight infants

BACKGROUND: Chronic lung disease (CLD) is a significant cause of neonatal morbidity and mortality despite advances in neonatal care. Ureaplasma urealyticum colonization of the lower respiratory tract has been associated with CLD, particularly in extremely low birth weight infants. Despite numerous studies demonstrating the pathogenicity of this organism, treatment remains controversial. This study examines neonates colonized with U. urealyticum in the lower respiratory tract and treated with erythromycin, as compared with noncolonized neonates. METHODS: A prospective cohort study of 124 neonates weighing <1000 g at birth, requiring endotracheal intubation and ventilation. Endotracheal aspirates were cultured for U. urealyticum and conventional bacteria twice weekly for the duration of endotracheal intubation. Infants colonized with U. urealyticum were treated with intravenous erythromycin. Maximal ventilatory requirements, CLD at Day 28 and 36 weeks postconception, duration of ventilation, oxygen dependency and hospital stay were documented. RESULTS: Twenty-two infants (18%) were identified as being U. urealyticum colonized in endotracheal aspirates. Colonization was significantly associated with younger maternal age, prolonged rupture of membranes, premature labor and vaginal delivery. Of colonized neonates 14% were delivered by cesarean section, with intact membranes. As compared with noncolonized infants, there were no statistically significant differences in chronic lung disease, duration of oxygen therapy or time to discharge. CONCLUSIONS: Seven published cohort studies of similar high risk populations where U. urealyticum-colonized infants did not receive erythromycin therapy, show a consistent association with CLD (pooled relative risk + 5.21; 95% confidence interval, 2.93 to 9.64). This association was not demonstrated in the current study and adds further weight to the need for a randomized controlled trial to be performed to evaluate this treatment regimen.     

Metabolic support of collecting duct transport

This study investigated the impact of deep diaphragmatic breathing (DB) on blood gases, breathing pattern, pulmonary mechanics and dyspnoea in severe hypercapnic chronic obstructive pulmonary disease (COPD) patients recovering from an acute exacerbation. Transcutaneous partial pressure of carbon dioxide (Ptc,CO2) and oxygen (Ptc,O2) and arterial oxygen saturation (Sa,O2), were continuously monitored in 25 COPD patients with chronic hypercapnia, during natural breathing and DB. In eight of these patients, breathing pattern and minute ventilation (V'E) were also assessed by means of a respiratory inductance plethysmography. In five tracheostomized patients, breathing pattern and mechanics were assessed by means of a pneumotachograph/pressure transducer connected to an oesophageal balloon. Subjective rating of dyspnoea was performed by means of a visual analogue scale. In comparison to natural breathing deep DB was associated with a significant increase in Ptc,O2 and a significant decrease in Ptc,CO2, with a significant increase in tidal volume and a significant reduction in respiratory rate resulting in increased V'E. During DB, dyspnoea worsened significantly and inspiratory muscle effort increased, as demonstrated by an increase in oesophageal pressure swings, pressure-time product and work of breathing. We conclude that in severe chronic obstructive pulmonary disease patients with chronic hypercapnia, deep diaphragmatic breathing is associated with improvement of blood gases at the expense of a greater inspiratory muscle loading.     

Twenty-month outcome in ventilator-dependent, very low birth weight infants born during the early years of dexamethasone therapy

We sought to examine the effect of the introduction of dexamethasone therapy on health, growth, and neurodevelopmental outcome in very low birth weight (VLBW) infants at 20 months of age. We compared outcomes in all 86 VLBW infants (mean birth weight 871 gm, mean gestational age 26.4 weeks) who were ventilator dependent on day 21 of life during the 2 years preceding October 1988 (period 1), when dexamethasone therapy became accepted clinical practice in our unit, with outcomes in all 124 infants (mean birth weight 891 gm, mean gestational age 26.9 weeks) with similar ventilator status during the subsequent 2 years (period 2). In addition, we compared outcomes in infants who received dexamethasone during period 2 with those in a concurrent cohort of less ill infants who were not given dexamethasone. There were no significant differences between periods 1 and 2 in mortality rates after 21 days (17% vs 21%), need for home oxygen (23% vs 25%), oxygen dependence at 20 months of corrected age (11% vs 10%), rate of neurosensory impairment (24% vs 25%), and mean Bayley Mental scores (81.5 vs 77.2) or Psychomotor Development Index (81.6 vs 71.1). Infants who received dexamethasone during period 2 had significantly more severe lung disease and poorer respiratory, growth, and developmental outcomes. We conclude that VLBW infants with ventilator-dependent chronic lung disease have very poor outcomes, even when treated with dexamethasone. More information is needed from prospective, randomized trials before dexamethasone can be accepted as routine therapy for chronic lung disease.     

Computer-controlled minute ventilation in preterm infants undergoing mechanical ventilation

INTRODUCTION: Computer-controlled minute ventilation (CCMV) continuously adjusts the ventilator rate to changes in spontaneous respiratory drive and pulmonary mechanics to maintain a preset total minute ventilation. HYPOTHESIS: We hypothesized that CCMV would maintain ventilation and oxygenation with fewer mechanical breaths than conventional intermittent mandatory ventilation in very low birth weight infants. METHODS: Very low birth weight infants in clinically stable condition who were undergoing mechanical ventilation were enrolled. The number of mechanical breaths, total and mechanical expiratory minute ventilation, mean airway pressure, oxygen hemoglobin saturation by pulse oximetry, and transcutaneous partial carbon dioxide and partial oxygen tensions were obtained during intermittent mandatory ventilation and CCMV (45 to 60 minutes) and compared by paired t test. RESULTS: Fifteen infants were studied. Birth weight (median, range) was 700 gm (550 to 1205 gm), gestational age 26 weeks (23 to 34 weeks), age 21 days (3 to 50 days). When switched from intermittent mandatory ventilation to CCMV, the number of mechanical breaths was reduced (15 +/- 2.8 to 8.6 +/- 2.9 breaths per minute, p < 0.001), leading to lower airway pressure (3.97 +/- 1.00 to 3.45 +/- 1.00 cm H2O, p < 0.001) and lower expiratory minute ventilation generated by the mechanical ventilator (116 +/- 31 to 65 +/- 28 ml/min per kilogram, p < 0.001), while total expiratory minute ventilation remained unchanged. Mean transcutaneous partial carbon dioxide and oxygen tensions, oxygen hemoglobin saturation, and the time spent within different oxygen hemoglobin saturation ranges did not differ between both ventilatory modes. CONCLUSION: CCMV maintained adequate ventilation and oxygenation with lower mechanical ventilatory support than IMV. CCMV may reduce barotrauma and chronic lung disease during long-term use.     

Immunohistochemical demonstration of c-myc oncogene product in middle ear cholesteatoma

Oxygen consumption at intermittent mandatory ventilation (IMV) rates of 10 and 20 breaths per minute was evaluated to determine whether a higher IMV rate in mechanically ventilated premature infants with apnea and respiratory insufficiency would reduce metabolic expenditure. Ten studies were performed in seven infants, with three infants studied twice after a trial of failed elective extubation. The mean birth weight was 952 +/- 183 kg (SD), and the mean postnatal age was 12 +/- 8 days (SD). Mean oxygen consumption per kilogram of body weight was not significantly related to pulmonary resistance, dynamic lung compliance, or resistive work of breathing. Mean oxygen consumption was not altered at the different IMV rates. The oxygen consumption difference at the two IMV rates was not significantly related to dynamic lung compliance, resistance, or work of breathing. These results demonstrate that mechanically dependent premature infants without bronchopulmonary dysplasia do not have significant alteration in oxygen consumption with changes in IMV. This finding suggests that there is no potential metabolic energy balance benefit in use of moderately higher IMV rates to achieve improved growth rates in this population of infants.     

Combined effects of antenatal corticosteroids and surfactant supplementation on the outcome of very low birth weight infants

Antenatal corticosteroids in preterm pregnancy may result in the reduction of the incidence of respiratory distress syndrome (RDS) and neonatal mortality. It is well known that postnatal use of surfactant in very low birth weight (VLBW) infants with RDS results in decreased neonatal morbidity and mortality. To evaluate the additive beneficial effects of combined antenatal corticosteroids and postnatal use of rescue surfactant on the outcome of VLBW infants, we retrospectively reviewed 286 maternal/infant charts of preterm infants with gestational ages 23 to 32 weeks and birth weights 501 to 1500 gm who were born at our institution from 1991 through 1994. Of the 87 (30%) infants who were treated with corticosteroids before birth, 41 (47%) had RDS, and of the 199 (70%) infants who were not treated with corticosteroids before birth, 162 (81%) had RDS (p < 0.001). The infants who had RDS and who were treated with corticosteroids before birth had a decreased incidence of pulmonary air leaks and a decreased need for diuretic therapy. In addition, they had a significant reduction in O2 requirement and ventilator settings as reflected by FIO2, mean airway pressure, ventilator rate, O2 index, and A-aDO2 before they received the first dose of rescue surfactant (p < 0.05 to p < 0.01) in contrast to other VLBW infants who had RDS and who were not treated with corticosteroids before birth. We conclude that antenatal corticosteroid therapy in threatened premature labor combined with the use of postnatal rescue surfactant is associated with a decreased incidence of RDS and may be beneficial for reducing the severity of RDS and improving the eventual outcome of VLBW infants.     

Pulmonary function changes after nebulised and intravenous frusemide in ventilated premature infants

AIMS: To compare the effects of a single dose of frusemide administered either intravenously or by nebulisation on pulmonary mechanics in premature infants with evolving chronic lung disease. METHODS: The effect of frusemide on pulmonary mechanics was studied at a median postnatal age of 23 (range 14-52) days in 19 premature infants at 24 to 30 weeks gestational age, who had been dependent on mechanical ventilation since birth. Frusemide (1 mg/kg/body weight) was administered, in random order, intravenously and by nebulisation, on two separate occasions 24 hours apart. Pulmonary function studies were performed before and at 30, 60, and 120 minutes after administration of frusemide. Urine was collected for six hours immediately before and for six hours after administration of frusemide. RESULTS: Nebulised frusemide increased the tidal volume 31 (SE 11.5)% and compliance 34 (SE 12)% after two hours, whereas no change in either was noted for up to two hours after intravenous frusemide administration. Neither intravenous nor nebulised frusemide had any effect on airway resistance. Six hour urine output increased from a mean (SE) of 3.3 (0.4) ml/kg/hour to 5.9 (0.8) ml/kg/hour following intravenous frusemide administration while nebulised frusemide had no effect on urine output. Urinary sodium, potassium, and chloride losses were also significantly higher after intravenous frusemide, whereas nebulised frusemide did not increase urinary electrolyte losses. CONCLUSION: Single dose nebulised frusemide improves pulmonary function in premature infants with evolving chronic lung disease without adverse effects on fluid and electrolyte balance.     

Doppler assessment of pulmonary artery pressure in neonates at risk of chronic lung disease

AIM: To evaluate the pulmonary artery pressure (PAP) change in very low birth-weight (VLBW) infants at risk of chronic lung disease (CLD). METHODS: The time to peak velocity:right ventricular ejection time (TPV:RVET) ratio calculated from the pulmonary artery Doppler waveform, which is inversely related to PAP, was used. The TPV:RVET ratio was corrected for different heart rate (TPV:RVET(c)). Seventy three VLBW infants studied on days 1, 2, 3, 7, 14, 21 and 28 were enrolled for the analysis. RESULTS: Twenty two infants developed CLD with a characteristic chest radiograph at day 28. Fifty one did not, of whom 17 were oxygen dependent on account of apnoea rather than respiratory disease, and 34 were non-oxygen dependent. The TPV:RVET(c) ratio rose progressively in all three groups over the first three days of life, suggesting a fall in PAP. In the oxygen and non-oxygen dependent groups, the mean (SD) ratio rose to 0.53 (0.09) and 0.57 (0.09), respectively, on day 7, then remained relatively constant thereafter. The CLD group rose more slowly after day 3 and had a significantly lower mean ratio from day 7 onwards compared with the other two groups (day 7: P < 0.001, days 14-28: P < 0.0001), and fell significantly from 0.47 (0.11) on day 7 to 0.41 (0.07) on day 28 (P = 0.01), suggesting a progressive rise in PAP. The mean (SD) ratios at day 28 of all infants were: CLD group 0.41 (0.07); oxygen dependent group 0.66 (0.15); and the non-oxygen group 0.67 (0.11). The CLD group had a significantly lower ratio than the oxygen dependent group and the non-oxygen group (P < 0.0001). Using the TPV:RVET(c) ratio of < 0.46, infants at risk of developing CLD could be predicted on day 7 (predictive value 82.8%, sensitivity 54.5%, specificity 94.1%). CONCLUSION: The non-invasive assessment of PAP using the TPV:RVET(c) ratio may be useful in the longitudinal monitoring of PAP change in VLBW infants, and for prediction of chronic lung disease.     

Human recombinant anti-Rh(D) monoclonal antibodies: improvement of biological properties by in vitro class-switch

The aim of this study was to investigate how intrauterine growth retardation affects body proportions in VLBW infants. The cohort consisted of 135 surviving and 80 deceased preterm infants weighing less than 1250 grams at birth. Gestational age varied between 24 and 36 weeks (mean age 29.7 and 27.5 weeks, respectively). Birth weight was more than 2 SD below the mean birth standard values in 32% of the surviving, and in 27% of the deceased infants. Reduction of weight, length and head circumference at birth was analysed using Z scores based on Swedish birth standards. Z scores of weight, length and head circumference were highly correlated in the surviving and the deceased infants (r = 0.78 to 0.94 and 0.65 to 0.97, respectively). Length was significantly more affected by growth retardation than weight. Weight and head circumference were proportionately reduced. Intrauterine growth retardation influences body proportions in VLBW infants differently than in larger preterm and term infants.     

Factors influencing successful discontinuance of mechanical ventilation after open heart surgery: a clinical study of 41 patients

Circulatory, respiratory, and metabolic variables were measured with a mobile clinical bedside unit in 41 patients during the first 48 hours after open heart surgery. Calculations were carried out off-line by a computer program. The variables were measured during controlled mechanical ventilation and compared with those obtained during spontaneous breathing and after resumption of mechanical ventilation; attempts at spontaneous breathing were categorized as successful or unsuccessful. The variables were compared before, during, and after the successful and the unsuccessful attempts at spontaneous breathing. In the series as a whole, the onset of spontaneous breathing was characterized by increases in cardiac output, radial arterial and pulmonary arterial pressures, and mixed venous oxygen tension (PVO2) and content (CVO2), as well as diminished arterial and mixed venous oxygen content differences (avDO2); no significant changes in oxygen consumption (VO2) were seen. Unsuccessful attempts disturbed the patient's physiological equilibrium by reducing oxygen delivery and not increasing VO2, while increasing ventilatory work. In general, resumption of controlled ventilation restored the physiological variables to their control conditions. Successful attempts at spontaneous breathing did not greatly affect the physiological variables. The indication for resumption of controlled ventilation after periods of spontaneous breathing is the combination of increased ventilatory work with diminished circulatory and respiratory functions.     

The need for inotropic support in a subgroup of infants with severe life-threatening respiratory syncytial viral infection

BACKGROUND: We experienced an unusual complication of life-threatening respiratory syncytial viral disease cardiovascular compromise. Life-threatening respiratory syncytial virus (RSV) infection has predominancy involved with ventilatory support for respiratory distress and/or failure. We performed a retrospective chart review of 20 consecutive infants admitted to the pediatric intensive care unit (PICU) for impending respiratory failure. METHODS: Seventeen required ventilatory support. As part of the infants' initial assessment, blood pressure, distal perfusion [capillary refill time (CRT) > or = 3 sec], decreased peripheral pulses, and peripheral mottling were used to determine cardiovascular compromise. These infants received volume resuscitation either at the referring facility or the PICU until euvolemia was obtained, as determined by central venous pressure (CVP) monitoring (between 3 to 7 cm H20). Nine of the 20 infants did not respond to volume resuscitation alone and required vasopressor support in the form of: Dopamine (7 patients, 5-10 micrograms/kg/min), Dobutamine (2 patients, 5-7 micrograms/kg/min), and one who expired required both Epinephrine (600 ng/kg/min) and Dopamine (10 micrograms/kg/min). The mean ages of these 9 patients were 6.2 +/- 3.4 weeks (range 3-12 weeks), the mean duration of ventilation was 7.2 +/- 4.1 days (range 4-12 days). The mean duration of pharmacologic support was 69.7 +/- 47 hours (range 14-168 hours). The mean ages of RSV+ infants not requiring inotropic support was 19.4 +/- 27.4 weeks (range 1-90 weeks), and mean duration of ventilation was 5.5 +/- 5.9 days (range 2-20 days). RESULTS: The inotrope treated patients were weaned from pharmacologic support prior to extubation, without any hemodynamic deficits. Our experience with this rather high incidence of hemodynamic complications during this RSV epidemic was unexpected. CONCLUSION: These results substantiate the fact that younger patients with RSV disease are at both greater risk for pulmonary complications and cardiovascular deterioration and may thus benefit from pharmacologic support.     

Physiologically based indices of volumetric capnography in patients receiving mechanical ventilation

Several indices of ventilatory heterogeneity can be identified from the expiratory CO2 partial pressure or CO2 elimination versus volume curves. The aims of this study were: 1) to analyse several computerizable indices of volumetric capnography in order to detect ventilatory disturbances; and 2) to establish the relationship between those indices and respiratory system mechanics in subjects with normal lungs and in patients with acute respiratory distress syndrome (ARDS), both receiving mechanical ventilation. We studied six normal subjects and five patients with early ARDS mechanically ventilated at three levels of tidal volume (VT). Respiratory system mechanics were assessed by end-expiratory and end-inspiratory occlusion methods, respectively. We determined Phase III slopes, Fletcher's efficiency index, Bohr's dead space (VD,Bohr/VT), and the ratio of alveolar ejection volume to tidal volume (VAE/VT) from expiratory capnograms, as a function of expired volume. Differences between normal subjects and ARDS patients were significant both for capnographic and mechanical parameters. Changes in VT significantly altered capnographic indices in normal subjects, but failed to change ventilatory mechanics and VAE/VT in ARDS patients. After adjusting for breathing pattern, VAE/VT exhibited the best correlation with the mechanical parameters. In conclusion, volumetric capnography, and, specifically, the ratio of alveolar ejection volume to tidal volume allows evaluation and monitoring of ventilatory disturbances in patients with adult respiratory distress syndrome.     

Infant physiological regulation and maternal risks as predictors of dyadic interaction trajectories in families with a preterm infant.

This longitudinal study examined predictors of rates of growth in dyadic interaction quality in children born preterm who did not experience significant neurological findings during neonatal intensive care unit (NICU) hospitalization. Multiple methods were used to collect data from 120 preterm infants (48% girls, 52% boys) and their mothers. Infant heart rate variability (HRV), gestational age, neonatal health, feeding route, and maternal socioeconomic (SES) risks were assessed at NICU discharge (mean of 36 weeks postconception). Mother–child interactions were observed at 4, 9, 16, and 24 months postterm and analyzed with hierarchical linear modeling. On average, children's quality of play, interest, and attention increased over time while their dysregulation and irritability decreased, whereas average maternal positive affect and involvement declined in quality (ps     

Predictors of extubation success and failure in mechanically ventilated infants and children

OBJECTIVE: To predict extubation success and failure in mechanically ventilated infants and children using bedside measures of respiratory function. DESIGN: Prospective collection of data. SETTING: A university-affiliated children's hospital with a 51-bed critical care unit. PATIENTS: All infants and children who were mechanically ventilated for at least 24 hrs, except neonates < or = 37 wks gestation and patients with neuromuscular disease. INTERVENTIONS: Bedside measurements of cardiorespiratory function were obtained immediately before extubation. MEASUREMENTS AND MAIN RESULTS: Extubation failure was defined as reintubation within 48 hrs of extubation in the absence of upper airway obstruction. Failure rates were calculated for different ranges (selected a priori) of preextubation measures of breathing effort, ventilatory support, respiratory mechanics, central inspiratory drive, and integrated indices useful in adults. Effort of spontaneous breathing was assessed by the respiratory rate standardized to age, the presence of retractions and paradoxical breathing, inspiratory pressure, maximal negative inspiratory pressure (maximal negative inspiratory pressure), inspiratory pressure/maximal negative inspiratory pressure ratio, and tidal volume indexed to body weight of a spontaneous breath. Ventilatory support was measured by the fraction of inspired oxygen (F10(2)), mean airway pressure, oxygenation index, and the fraction of total minute ventilation provided by the ventilator. Respiratory mechanics were assessed by determination of peak ventilatory inspiratory pressure and dynamic compliance. Central inspiratory drive was assessed by mean inspiratory flow. Frequency to tidal volume ratio and the compliance, rate, oxygenation, and pressure indexed to body weight, the integrated indices useful in predicting extubation failure in adults, were also calculated. Thirty-four of the 208 patients who were studied were reintubated for an overall failure rate of 16.3% (95% confidence interval 11.3% to 21.4%). The reasons for reintubation were poor effort (n = 8), excessive effort (n = 14), altered mental status or absent airway reflexes (n = 2), cardiovascular instability (n = 3), inadequate oxygenation (n = 3), respiratory acidosis (n = 3), and undocumented (n = 1). Extubation failure increased significantly with decreasing tidal volume indexed to body weight of a spontaneous breath, increasing F10(2), increasing mean airway pressure, increasing oxygenation index, increasing fraction of total minute ventilation provided by the ventilator, increasing peak ventilatory inspiratory pressure, or decreasing mean inspiratory flow (p < .05). Dynamic compliance showed a trend of increasing failure rate with decreasing dynamic compliance but did not reach statistical significance (p = .116). Respiratory rate standardized to age, inspiratory pressure, maximal negative inspiratory pressure, inspiratory pressure/maximal negative inspiratory pressure ratio, frequency to tidal volume ratio, and compliance, rate, oxygenation, and pressure did not show any trend in failure rate with increasing or decreasing values. Threshold values that defined a low risk (< or = 10%) and a high risk (> or = 25%) of extubation failure could be determined for tidal volume indexed to body weight of a spontaneous breath, F10(2), mean airway pressure, oxygenation index, fraction of total minute ventilation provided by the ventilator, peak ventilatory inspiratory pressure, dynamic compliance, and mean inspiratory flow. Neither a low nor a high risk of failure could be defined for frequency to tidal volume ratio or the compliance, rate, oxygenation, and pressure (CROP) index. CONCLUSIONS: Bedside measurements of respiratory function can predict extubation success and failure in infants and children. Both a low risk and a high risk of failure can be determined using these measures. Integrated indices useful in adults do not reliably predict extubation success or failure in     

Rehabilitation of patients admitted to a respiratory intensive care unit

OBJECTIVE: Pulmonary rehabilitation has been shown to be of benefit to clinically stable patients with chronic obstructive pulmonary disease (COPD). This study examined the effect of pulmonary rehabilitation on some physiologic variables in COPD patients recovering from an episode of acute respiratory failure. DESIGN: A prospective, randomized study. SETTING: A respiratory intensive care unit (RICU). PATIENTS: Eighty COPD patients recovering from an episode of acute respiratory failure were randomized in a 3:1 fashion to receive stepwise pulmonary rehabilitation (group A, n=60 patients) or standard medical therapy (group B, n=20 patients). MAIN OUTCOME MEASURES: Improvements in exercise tolerance, sense of breathlessness, respiratory muscle function, and pulmonary function test values were measured, respectively, by exercise capacity (6-minute walking distance [6MWD]), dyspnea score (Visual Analog Scale [VAS]), maximal inspiratory pressure (MIP), forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC). INTERVENTIONS: Group A received pulmonary rehabilitation that consisted of passive mobilization (step I), early deambulation (step II), respiratory and lower skeletal muscle training (step III), and if the patients were able, complete lower extremity training on a treadmill (step IV). Group B received standard medical therapy plus a basic deambulation program. RESULTS: Sixty-one of 80 patients were mechanically ventilated at admission to the unit and most of them were bedridden. Twelve of the 60 group A patients and 4 of the 20 group B patients died during their RICU stay, and 9 patients required invasive mechanical ventilation at home after their discharge. The total length of RICU stay was 38+/-14 days for patients in group A versus 33.2+/-11 days for those in group B. Most patients from both groups regained the ability to walk, either unaided or aided. At discharge, 6 MWD results were significantly improved (p < .001) in Group A only. MIP improved in Group A only (p < .05), while VAS scores improved in both groups, but the improvement was more marked in group A (p < .001) than in group B (p < .05). CONCLUSIONS: COPD patients who were admitted to a RICU in critical condition after an episode of acute respiratory failure and who, in most cases, required mechanical ventilation benefited from comprehensive early pulmonary rehabilitation, compared with patients who received standard medical therapy and progressive ambulation.     

Oxygen cost of breathing and weaning process in newborn infants

Newborn infants may have a high oxygen cost of breathing (OCB) at the time of being weaned from mechanical ventilation. We hypothesized that this increase in oxygen consumption (V'O2) could be reduced by using certain weaning ventilatory modes. We designed a study to assess V'O2 during three weaning ventilatory modes: patient triggered ventilation, synchronous intermittent mandatory ventilation (SIMV) and continuous positive airway pressure in 16 newborn infants before being weaned from mechanical ventilation In seven infants whose OCB was high. V'O2 was not significantly different between CV and PTV (8.9+/-0.6 versus 9.5+/-0.8, respectively) whereas it tended to increase to 10.8+/-1.1 mL x min(-1) x kg(-1) during SIMV and increased significantly to 11.9+/-0.8 mL x min(-1) x kg(-1). In the other nine infants whose OCB was normal, no significant variation of V'O2 was observed. Patient triggered ventilation was a weaning ventilatory mode that significantly reduced the increase in oxygen consumption observed in infants with a high oxygen cost of breathing, as compared to synchronous intermittent mandatory ventilation or continuous positive airway pressure. Further investigations in newborn infants with a high oxygen cost of breathing should be performed prior to routine use of patient triggered ventilation.