Measurement of lung volumes and pulmonary mechanics during weaning of newborn infants with intractable respiratory failure from extracorporeal membrane oxygenation

Newborn infants with intractable respiratory failure who require extracorporeal membrane oxygenation (ECMO) experience diffuse pulmonary atelectasis shortly after initiation of ECMO. Atelectasis is likely due to the primary lung injury and the reduction of applied inspiratory ventilator pressure when the respirator settings are changed to the “rest settings.” These pathophysiologic changes result in a decrease in lung compliance and lung volumes. We hypothesized that improving lung functions observed during ECMO and indicated by an increase in lung volumes will predict successful weaning from ECMO. Sixteen infants (mean SEM: gestational age, 40.3 ± 0.3 weeks; birth weight, 3.5 ± 0.1 kg) with meconium aspiration syndrome (n = 13), sepsis (n = 2), and persistent pulmonary hypertension (n = 1) were studied. We measured passive respiratory system mechanics and lung volumes initially during full ECMO support (115 ± 18 h on ECMO, Study I), and then within 24 h prior to weaning from ECMO (Study 11). Respiratory system compliance (C_rs), respiratory system resistance (Rrs), functional residual capacity (FRC), and tidal volume (V_T) were measured. Prior to Study I lung volumes were too small to be detected. C, increased between Study I and Study II (0.41±0.05 to 0.63±0.05 mL/cmH₂O/kg, P < 0.05), and V_T, increased between Study I and Study II (5.6 ± 0.6 to 10.4 ± 0.8mL/kg, P = 0.0005). FRC increased from 3.6 ± 1.0 to 7.9 ± 0.9mL/kg(P = 0.0001). There was no change in R_rs (88±8 to 89 ± 6 cm H₂O/Us, P = 0.9). The combination of C_rs > 0.5 mL/cmH₂O/kg and FRC > 5 mL/kg was a better predictor (P = 0.0002) of readiness to wean from ECMO than either C (>0.5 mL/cmH₂O/kg, P = 0.057) or FRC (>5 mL/kg, P = 0.007) alone. The combination of FRC and C_rs had a sensitivity of 73.3% and specificity of 100% for successful decannulation. We conclude that repeated measurements of FRC and C_rs can assess lung recovery and may assist in establishing criteria for successful weaning from ECMO. Pediatr Pulmonol. 1995; 20:145–151 . © 1995 Wiley-Liss, Inc.     

Changes in lung mechanics following sighs in premature newborns without lung disease

Sighs, the interspersed breaths of larger tidal volume (V_T) than those preceding or following them, occur more frequently in the newborn than in adults. It has been postulated that the sigh augments functional residual volume (FRC), increases lung compliance (CJ, and recruits atelectatic alveoli. Since the premature infant has relatively low FRC, we hypothesized that sighs might be more frequent in these babies and that C_L could be shown to change before and/or after a sigh. We studied 14 premature infants (gestational age, 30 ± 2.2 weeks; mean ± SD) without lung disease during quiet sleep. Minute ventilation (V_E) was measured by pneumotachography and pleural pressure changes via a water-filled catheter in the esophagus. In the 78 sighs examined, the incidence was 0.71 sighs/min, similar, to previous reports for full-term newborns. There was no change in respiratory frequency, V_T/V_E, nor mean inspiratory flow (V_T/T_t, where T_t is the inspiratory time) before or after the event. The volume of the sigh increased from 7.8 ± 0.2 mL/kg to 21.5 ± 0.5 mL/kg, in concert with an increase in breath duration (T_TOT) from 0.98 ± 0.02 ± to 2.56 ± 0.12 s, resulting in an unchanged V_E, V_T/T_I). and respiratory duty cycle (T_I/T_TOT/). This suggests that the increased V_T was matched by a prolongation in both T_I and T_TOT. Following the sigh, C_L increased from 1.43 ± 0.13 cmH₂O/kg to 1.66 ± 0.27 cmH₂O/L/s/kg (paired t-test, P < 0.001) whilst the lung resistance R_L, fell from 62 ± 8 cmH₂O/L/s/kg to 55 ± 3.8 cmH₂O/L/s/kg (P < 0.05). As reflected by the end—expiratory volume (EEV), FRC did not change. This stability of FRC, coupled with the increase in C_L and fall in R_L, suggests a recruitment of atelectatic acini with a redistribution of lung volume, such that the previously atelectatic and overdistended acini achieve a more optimal pressureivolume relationship following a sigh. Pediatr Pulmonol. 1994; 17:22–25. © 1994 Wiley-Liss, Inc.     

Compliance of the respiratory system in newborn infants pre- and postsurfactant replacement therapy

Surfactant administration causes a rapid and dramatic improvement in gas exchange, but paradoxically, studies have failed to show an improvement in the mechanical properties of the lung. We have measured dynamic and static (passive flow-volume technique) compliance before and after a single dose of bovine lipid extract surfactant in 22 premature infants with RDS. This had no effect on the measured dynamic compliance. In contrast, surfactant significantly increased static compliance from 0.41 ± 0.02 to 0.55 ± 0.04 mL/cm H₂,O/kg. This improvement was the result of a substantial recruitment of lung volume after surfactant administration. This led us to reduce ventilator pressures, which produced an increase in both dynamic and static compliance, but did not recruit additional volume. We conclude that surfactant causes a substantial increase in static compliance due to volume recruitment, which is consistent with reports of increase in the measured FRC. However, despite this improvement, the compliance is still below our normal range. © 1993 Wiley-Liss, Inc.     

Continued pulmonary recovery observed after discontinuing extracorporeal membrane oxygenation

Extracorporeal membrane oxygenation (ECMO) is a valuable therapy for the treatment of reversible lung disease in neonates. Associated with this treatment, however, are risks for complications that increase with the duration of therapy. We evaluated alveolar-arterial oxygen tension difference P pulmonary compliance (C_L), and functional residual capacity (FRC) in 20 infants immediately after ECMO was discontinued, and again 24 hours thereafter. We measured C, by pnemotachography and eosphageal manometry and FRC by helium dilution. Mean (±SEM) values for C_L and FRC increased (C_L from 0.28 ± 0.02 to 0.35 ± 0.03 mL/cmH₂O)/kg and FRC from 18.6 ± 1.4 to 22.2 ± 1.1 mL/kg; P < 0.05), and P and the oxygenation index (OI) decreased (200 ± 19 to 169 ± 14 mm Hg and 6.9 ± 0.44 to 5.4 ± 0.5, respectively; P < 0.02), over the 24 hour period following ECMO. Nineteen of 20 infants experienced improvement in at least two of these parameters. Improvements were found to be greatest in the infant with the worst lung function immediately after discontinuing ECMO, and in the ten infants who had not received pancuronium bromide for inducing skeletal muscle paralysis, following decannulation from ECMO. These data indicate that improvement in lung function following ECMO will generally continue over the 24 hour period following the termination of cardiopulmonary bypass, and that borderline pulmonary status may not preclude discontinuation of bypass therapy. Pediatr Pulmonol. 1994; 17:143–148. © 1994 Wiley-Liss, Inc.     

Continuous negative extrathoracic pressure versus positive end-expiratory pressure in piglets after saline lung lavage

Recent reports have suggested that substituting continuous negative extrathoracic pressure (CNEP) for positive end-expiratory pressure (PEEP) may result in clinical benefits to infants with pulmonary disease. Other studies have suggested potential hemodynamic advantages. We compared the effects of CNEP and PEEP in 13 mechanically ventilated newborn piglets after acute lung injury induced by saline lavage. The piglets were instrumented, salinelavaged, and exposed to 15 minute periods of incremental CNEP (–3, –6, –9, –12 cmH₂O) (n = 7) or PEEP (3, 6, 9, 12 cmH₂O) (n = 6). We measured and/or calculated dynamic lung compliance (C_Ldyn), lung resistance (R_L), end-expiratory lung volume (EELV), blood gases, cardiac output (CO), heart rate (HR), transmural vascular pressures, and pulmonary and systemic vascular resistance. Pulmonary function abnormalities after saline lavage included decreased P_ao2, C_Ldyn, EELV, and increased P_aco₂ and R_L (P < 0.05). Except for decreased CO, lung inflation with both CNEP and PEEP resulted in large increases in P_aO₂ without major pulmonary or hemodynamic effects. Other than differences in EELV at 3, 6, and 9 cmH₂O distending pressure, there were no differences in pulmonary function or hemodynamics between sequences of incremental CNEP and PEEP. We conclude that CNEP and PEEP are physiologically equivalent in this model of acute lung injury. Pediatr Pulmonol. 1994; 17:161–168. © 1994 Wiley-Liss, Inc.     

Pulmonary mechanics in ventilated preterm infants with respiratory distress syndrome after exogenous surfactant administration: A comparison between two surfactant preparations

The effects of two surfactant preparations on lung mechanics have been studied on 24 ventilated premature infants with respiratory distress syndrome (RDS): 13 were given artificial surfactant (Exosurf Neonatal, Burroughs–Wellcome) and 11 natural porcine surfactant (Curosurf, Laboratoire Serono France). Measurements of respiratory system compliance (C_dyn C_rs) and resistance (R_rs) were performed immediately before surfactant administration and repeated 6, 18, 24, 48, and 72 hours later. With Exosurf treatment, 6 hours after surfactant administration inhaled O₂ concentration (F_IO₂) could be lowered from (0.72 ± 0.20, to 0.62 ± 0.33; P < 0.05), whereas (C_rs)did not change (0.37 mL/cmH₂O/kg, ± 0.14 vs. 0.39 ± 0.12, NS). After 24 hours and during the following days a significant increase in (C_rs) occurred (24 hours post-Exosurf: 0.51 ± 0.18, P < 0.05). With Curosurf treatment, the improvement in oxygenation was greater and F_IO₂ could be lowered much more after 6 hours (from (F_IO₂), 0.78 2 ± 0.23 to 0.34 ± 0.11, P < 0.01). This was associated with an increase in (C_rs) (from 0.39 ± 0.09 to 0.59 ± 0.17, P < 0.05). During the following days, (C_rs) was significantly higher in the group treated with Curosurf. Resistance was not altered by the type of surfactant preparation used except after 72 hours, when R_rs increased in the group treated with Exosurf. In conclusion, Curosurf appears to be more effective than Exosurf with regard to immediate pulmonary changes in ventilator treated premature infants with RDS. A rapid increase in (C_rs) after Curosurf treatment indicates that recruitment of new functional areas of the lung is likely to be associated with a stabilization of small airways and alveolar units. Pediatr Pulmonol. 1994;18:273–278 © Wiley-Liss, Inc. © Wiley-Liss, Inc.     

Assessment of pulmonary function in the early phase of ARDS in pediatric patients

Scant data are available on lung function in acute respiratory distress syndrome (ARDS) in pediatric patients. We measured respiratory mechanics by single-breath occlusion and maximum expiratory flow-volume curves by forced deflation in ten critically ill infants with clinical ARDS. Ten mechanically ventilated infants without lung disease served as the control group. To assess the severity of the lung injury in the infants with ARDS, we modified an adult scoring system that calculates a score (from 0 to 4; >2.5 indicates severe lung injury) based on the extent of chest radiographic changes, degree of hypoxemia, amount of positive end-expiratory pressure (PEEP), and total respiratory system compliance. The lung injury scores of our patients were in the range of 2.75 to 3.75. The lung injury scores of the control group were zero. The predominant alteration in lung function was restrictive, as characterized by a significant decrease in total respiratory system compliance (0.41 ± 0.13 ml/cmH₂O/kg versus 1.12 ± 0.16 ml/cmH₂O/kg of controls; P < 0.001) and forced vital capacity (21.5 ± 6.5 ml/kg versus 59.2 ± 6.3 ml/kg of controls; P < 0.001). Maximum expiratory flow rates at 10% forced vital capacity were significantly increased (23.6 ± 20.1 ml/kg/sec versus 8.4 ± 2.5 ml/kg/sec of controls; P < 0.05), confirming the absence of any significant obstructive abnormalities. The passive expiratory flow-volume curves were curvilinear and convex in shape, indicating inhomogeneous lung pathology. The inhomogeneous distribution of lung injury in ARDS restricts the validity of respiratory mechanics measurements that rely on a single-compartment model. However, the forced deflation technique allows accurate spirometric assessments of the severity of restrictive (and obstructive) lung function changes in intubated infants with severe ARDS. Such measurements can be incorporated into lung injury scoring systems to classify the severity of the disease process for the purpose of outcome evaluation and to evaluate the effect of therapeutic interventions. Pediatr. Pulmonol. 1997; 23:169–175 © 1997 Wiley-Liss, Inc.     

Pulmonary function following positive pressure ventilation initiated immediately after birth in infants with respiratory distress syndrome

Cardiopulmonary function following positive pressure ventilation, initiated immediately after birth, was evaluated in 10 very low birthweight infants with respiratory distress syndrome (RDS; RDS infants). Multiple gas rebreathing methodology was used to measure functional residual capacity (FRC), diffusing capacity of the lung for carbon monoxide (DLCO) and effective pulmonary capillary blood flow (Qeff) at 2, 24, and 72 hr of age. Cardiopulmonary function variables were also measured at 2 hr of age in 10 infants of similar birthweight who did not have RDS (non-RDS infants). In RDS infants, mean FRC at both 2 hr of age (15 mL/kg or 0.42 mL/cm) and 24 hours of age (20 mL/kg or 0.54 mL/cm) was less than published predicted values for healthy infants and significantly less than values in non-RDS infants at 2 hours of age (29 mL/kg or 0.8 mL/cm). By 72 hr of age, mean FRC in RDS infants rose to predicted. At 2 and 24 hours of age, mean Qeff in RDS infants (41 and 38 mL/min/kg, respectively) was below predicted, as well as below the value observed in non-RDS infants at 2 hr of age (62 mL/min/kg). in RDS infants. DLCO remained well below published predicted values throughout the first three days of life. We conclude that early aggressive respiratory therapy does not result in the establishment of normal lung volumes during the first day of life, but it does so by 3 days of age. However, in spite of intubation immediately after birth and the application of continuous positive pressure ventilation during the first 3 days of life, very low birthweight infants with RDS continue to have significant alteration in lung function, evidenced by impaired diffusing capacity of the lung and low arterial-alveolar oxygen tension ratios.     

Efficacy of surfactant therapy in infants managed with CPAP

Surfactant rescue therapy can be utilized effectively early in the course of respiratory distress syndrome (RDS) in infants weighing > 1,000 g and treated exclusively with continuous positive airway pressure (CPAP) therapy. Thirteen infants (BW, 1,774 ± 580 g; GA, 31 ± 3 weeks) comprising the CPAP/SURFACTANT group were compared with 12 infants (BW, 1,753 ± 556 g; GA, 31 ± 2 weeks) who comprised the intermittent mandatory ventilation (IMV)/ surfactant group, and with 14 infants (BW, 1,776 ± 332 g; GA, 32 ± 2 weeks) treated with CPAP before surfactant was clinically available. A 5 mL/kg dose of Exosurf Neonatal (Burroughs-Wellcome) was administered to infants intratracheally when the F_iO₂ requirement reached 0.40 to maintain the PO₂ above 50 torr. Infants in the CPAP/surfactant group were intubated solely for surfactant administration and extubated within 18 ± 6 min of treatment. The CPAP/surfactant group was treated at a mean age of 12.3 ± 9.3 h, and the IMV/surfactant group at 10.2 ± 9.8 h. Alveolar-arterial oxygen gradient (AaDO₂), oxygenation index (OI), and mean airway pressure (MAP) were determined immediately before and after surfactant therapy, and at comparable times for the CPAP- only group. A significant difference was found in pre-treatment AaDO₂, OI, and MAP between the CPAP/ surfactant group and IMV/surfactant group, but not between the CPAP/surfactant group and the CPAP-only group. Similarly, a significant difference in AaDO₂, OI, and MAP continued post-treatment was noted. However, a significant difference was also found at this time between the CPAP/surfactant group and the CPAP- only group. In addition, a significant difference was noted in AaDO₂ and OI pre- and post-treatment within each surfactant-treated group. Furthermore, in the CPAP-only group AaDO₂ and OI actually worsened (212 ± 70 vs. 239 ± 68; 4.0 ± 1 vs. 4.5 ± 2, respectively). There was a significant reduction in the duration of oxygen therapy (3 ± 2 vs. 5 ± 2 vs. 4.5 ± 2 days, respectively) as well as in the total days of hospitalization (30 ± 10 vs. 42 ± 15 vs. 43 ± 12 days, respectively). We conclude that in this small group of infants surfactant administration was effective and safe. It appeared to improve the course of RDS and shorten the duration of oxygen exposure and days of hospitalization. Pediatr Pulmonol. 1995; 20:172–176 . © 1995 Wiley-Liss, Inc.     

Mechanics of respiration in healthy children 6 to 15 years of age

Dynamic lung compliance (C₁dyn) and total pulmonary flow resistance (R₁) have been measured in 183 healthy children (99 boys and 84 girls), 6 to 15 years of age. The breath by breath variation of C₁dyn is 17.5% (±7.8%) in boys and 16.9% (±8.0%) in girls. Cardiac pulsations artefacts on the record of the intraoesophageal pressure variations (ΔP_oes) were considered mostly responsible for these C₁dyn variations. The breath by breath variation of R₁ is 16.1% (±7.0%) in boys and 17.0% (±7.1%) in girls, mainly caused by variations of the upper airway resistance. C₁dyn and R₁ values are well correlated to standing height if the variables are expressed in logarithmic terms. The taller the child, the larger is C₁dyn and the smaller is R₁. The scattering of the individual values is large. Compared to the results published in literature, C₁dyn is larger at the same standing height in the present study: in a child of 120 cm standing height, C₁dyn is 71 ml/cmH₂O; in a child of 160 cm standing height, C₁dyn is 139 ml/cmH₂O. But compared to static lung compliance values in healthy children, the difference is small. Differences in lung volumes in boys and girls explain differences in C₁dyn. FRC specific lung compliance (C₁dyn/FRC) was found to be identical in boys and girls. The mean value of C₁dyn/FRC (0.078 ml/cmH₂O/ml) is larger than the corresponding values, published in literature, reflecting the larger C₁dyn values in the present results. But FRC specific static lung compliance, previously published on healthy children, corresponds well to the C₁dyn/FRC values in the present results. As shown by FRC specific static lung compliance, the taller is the child, the smaller is C₁dyn/FRC, the correlation coefficient between standing height and C₁dyn/FRC is small (r=0.28 in girls and 0.19 in boys), only significant in girls (p=0.019), reflecting the smaller scattering of the individual C₁dyn values around the regression line in girls. There is no proof, that the compliance per unit of lung volume is identical whatever the age, as discussed in literature.     

Influence of lung volume hysteresis on collateral resistance in intact dogs

Collateral resistance (Rcoll) is highly lung volume dependent. We studied 12 dogs in an attempt to evaluate the influence of hysteresis on this volume dependency. Rcoll measurements were obtained at baseline and at different lung volumes as modified by the application of negative or positive extrathoracic pressure (ETP) in an iron lung. ETP was modified in 5 cmH₂O steps from +20 to -25 cmH₂O) and back to +20 cmH₂O on the first day (cycle 1), and, in 4 of these dogs, from -25 to +20 cmH₂O and back to -25 cmH₂O on a second day (cycle 2). The behavior of Rcoll for both cycles was the same in all dogs, varying inversely with the changes in end-expiratory lung volume (EELV). All dogs presented a similar pattern: during cycle 1, for a same lung volume, Rcoll was much higher during the deflation limb than during the inflation limb. For cycle 2, Rcoll at a given lung volume was similar whether measured during the inflation or deflation limb. Changes in EELV were higher for any given negative ETP during the deflation than during the inflation limb of the pressure cycles (e.g., for the 4 dogs who had both cycles, at -15 cmH₂O ETP of cycle 2 the increase in EELV was 1167±121 ml during deflation and 525±102 ml during the subsequent inflation [mean±SEM]). In conclusion, the effects of hysteresis on Rcoll and on lung volumes are similar, except at low lung volumes during the deflation limb of cycle 2. This latter finding could be due to the closure of collateral pathways at a higher lung volume during deflation than during inflation.     

The effects of reversing distending pressure sequences in the neonatal piglet

We studied different sequences of lung inflation in ventilated newborn piglets with normal lungs in order to determine the effects of sequence, magnitude and duration of distending pressure on pulmonary function, and/or hemodynamics. End-expiratory pressure was varied using a continuous negative extrathoracic pressure (CNEP) device. Three groups of ventilated piglets with normal lungs were exposed to 2 cmH₂O increments of CNEP from ?2 to ?12 cmH₂O and to decrements from ?12 to ?2 cmH₂O or to only -6 cmH₂O. Lung inflation sequence, magnitude of inflation pressure, and duration of inflation had significant effects on end-expiratory lung volume and lung compliance at numerically equivalent pressure levels. End-expiratory lung volume and lung compliance varied (at four and five of six inflation pressures studied) by as much as 68% and 104%, respectively. Hemodynamic effects of the lung inflation sequence were more variable; those found to be different at numerically equivalent pressure levels were associated with changes in lung compliance and ventilation. Differences in pulmonary mechanics can best be explained by the effects of lung inflation on alveolar recruitment versus overinflation. Pediatr Pulmonol. 1994; 17:97–105 . © 1994 Wiley-Liss, Inc.     

Assessment of forced expiratory volume — time parameters in detecting histamine-induced bronchoconstriction in wheezy infants

A new technique recently introduced allows the measurement of infant lung function from lung volumes raised by a pump prior to generation of forced expiratory flow-volume (FEFV) curves. Forced expiratory volume-time (FEV₁) parameters rather than traditional flow parameters are used. The aim of this study was to assess the usefulness of FEV, parameters in detecting airway responsiveness to histamine in recurrently wheezy infants. Ten infants (age 7–18 months) sedated with 80 mg/kg chloral hydrate underwent a histamine inhalation challenge. Throughout the challenge FEFV curves were generated from end-tidal inspiration. Raised FEFV curves, from a lung volume preset by 15 cmH₂O inflation pressure, were gathered at baseline and after the final concentration of histamine. The mean fall from baseline was 47% in maximal flow at functional residual capacity (VmaxFRC) (P < 0.0005), 15.5% in FEV_0.5 (P < 0.000l), 13.5% in FEV_0.75 (P < 0.005), and 11.0% in FEV_1.0 (P = 0.057), after the final concentration of histamine delivered. Tidal volume and inspiratory volume reached above FRC between pre- and posthista-mine did not change. Mean oxygen saturation fell significantly from 97 to 93%. We conclude that FEV₁ parameters adequately detect reduced lung function during histamine-induced bronchoconstriction and appear suitable for histamine challenge testing in infants. © 1993 Wiley-Liss, Inc.     

Pulmonary sequelae in infants treated with extracorporeal membrane oxygenation

The decision to place an infant on extracorporeal membrane oxygenation (ECMO) is based on predictions of expected morbidity and mortality. One unknown factor is the relationship between pre-ECMO pulmonary dysfunction and on barotrauma and post-ECMO pulmonary sequelae. To determine whether placement of infants on extracorporeal membrane oxygenation (ECMO) early is associated with less subsequent pulmonary dysfunction than placing infants on EMCO later, we evaluated pulmonary function in 25 neonates prior to ECMO, when the infants had come off EMCO, and at the time of nursery discharge. Pulmonary resistance (R) and compliance (C_L) were determined by a pneumotachograph and esophageal manometry, and functional residual capacity (FRC) was determined by a helium dilution method. Maximal expiratory flow (VmaxFRC) was determined by thoracic compression at the time of discharge. Infants were assigned to an early ECMO group (<36 hours of age, n = 12), or a late ECMO group (>36 hours of age, n = 13). When first evaluated, the early group had a higher oxygenation index than the late group (mean value, 63 versus 48), but initial pulmonary function measurements were not different between the two groups. In the early group mean C_L increase from 0.20 to 0.36 ml/cmH₂O/kg, FRC increased from 7 to 20 ml/kg, and mean R decreased from 107 to 61 cmH₂O/L/sec between the initial study and immediately after ECMO. In the late group, only FRC increased from a mean of 8 to 20 ml/kg. C_L and FRC increased from post-ECMO to discharge in both groups (mean C_L from 0.36 to 0.76 ml/cmH₂O/kg in the early group, and from 0.30 to 0.79 in the late group). Mean FRC increased from 20 to 26 ml/kg in the early group, and from 20 to 25 ml/kg in the late group. VmaxFRC was lower in the late than the early group at discharge (mean, 1.14 versus 1.58 L/sec; P < 0.05). While both groups of infants had minimal pulmonary dysfunction at discharge, the infants placed on ECMO early had evidence of slightly less airway dysfunction despite a higher initial oxygenation index than the infants placed on ECMO late. Pediatr Pulmonol. 1997; 23:31–38. © 1997 Wiley-Liss, Inc.     

Effect of positive end-expiratory pressure on respiratory compliance in children with acute respiratory failure.

We studied the effect of positive end-expiratory pressure (PEEP) on the compliance of the respiratory system (Crs) in 25 children (age, 3 weeks to 10 years) requiring mechanical ventilation. Functional residual capacity (FRC) measurements were performed at 2 cm H2O increments, from 0 to 18 cm H2O of PEEP, and the FRC values were regressed versus PEEP. Static Crs, Crs/kg, and specific compliance (Crs/FRC) were calculated for each PEEP level. When FRC normality was reached Crs/kg improved in 15/25 (60%) patients but decreased in 2/25 (8%). Overall, Crs/kg increased from a mean +/- SE of 0.94 +/- 0.09 to 1.35 +/- 0.13 mL/cm H2O/kg (P = 0.003) and Crs/FRC from a mean +/- SE of 0.067 +/- 0.006 to 0.077 +/- 0.007 mL/cm H2O/mL (P = 0.057). The maximum compliance (mean Max Crs/kg, 1.56 +/- 0.12 mL/cm H2O/kg, and mean Max Crs/FRC, 0.089 +/- 0.005 mL/cm H2O/mL) was significantly higher than the compliance at the clinically chosen PEEP level and the compliance at the PEEP that normalized FRC. Maximum compliance was achieved within 4 cm H2O of the PEEP that normalized FRC. In 14/25 (60%) of cases the PEEP at maximum compliance coincided with the PEEP that resulted in FRC normalization. We concluded that static respiratory compliance improves in most (but not all) children with acute respiratory failure when FRC is normalized. Static respiratory compliance reaches maximum levels at PEEP values that are close (but not equal) to those that result in FRC normalization. Thus, assessment of the effect of PEEP on compliance is required in individual patients.     

Comparison of helium dilution and nitrogen washout measurements of functional residual capacity in premature infants

Comparison has been made of measurements of functional residue capacity (FRC) by a helium gas dilution (He) and a nitrogen washout (N₂) technique. Twenty infants (median gestational age, 29.5 weeks) were studied at a median postnatal age of 25 days. No infant was oxygen dependent. The coefficient of repeatability of FRC (He) was 6.4 mL/kg and of FRC (N2), 6.3 mL/kg. The coefficient of repeatability of the two methods combined was 13.8 mL/kg. In 10 infants the results of two techniques differed by more than 20% of the mean FRC; those infants were born at a significantly earlier gestation than the rest of the cohort (P < 0.01). We conclude that, except in very immature infants, techniques for measuring FRC (He) and FRC (N₂) yield reproducible and comparable results in convalescent premature infants. Pediatr Pulmonol. Pediatr Pulmonol. 1993; 16:197–200. © 1993 Wiley-Liss, Inc.     

Effect of maternal smoking during pregnancy on passive respiratory mechanics in early infancy

We studied the effect of prenatal maternal cigarette smoking on passive expiratory mechanics in 53 healthy infants tested early in infancy (mean ± SD, 5.1 ± 1.5 weeks). Maternal smoking was measured by: 1) questionnaire reports of the number of cigarettes smoked per day; and 2) urine cotinine concentrations (corrected for creatinine) at each visit. Respiratory system mechanics were assessed by the single-breath occlusion-passive-flow-volume maneuver. In ten infants born to smoking mothers the time constant of the respiratory system was 23% reduced [0.34 vs. 0.44 s; 95% confidence interval (CI), ?45% + 1%; P = 0.06]. This was related to an estimated 13% decrease in respiratory system compliance (4.86 vs. 5.62 Ml/cmH₂O; 95%Cl, ?33% + 6%; P = 0.18) and a 10% reduction in respiratory system resistance (0.073 vs. 0.081 cmH H₂O/mL/s; 95%Cl, ?42% + 22%; P = 0.56). Functional residual capacity (FRC), measured by helium-dilution, was also decreased by 13% (78 vs. 90 mL; 95%Cl, ?27% + 0.3%; P = 0.06) in smoke-exposed infants. Forced expiratory flow rates at FRC obtained by thoraco-abdominal compression were reduced by 28% in infants of smoking mothers (VFRc, 99 vs. 138 rnlis; 95%Cl, ?54% + 2%; P = 0.04), as reported previously in a larger sample from this population. This study was limited by small numbers of infants exposed to smoking during pregnancy and by ethnic imbalance among the smoking-exposed and unexposed groups. Nevertheless, it suggests that the diminished forced expiratory flows observed in infants exposed in utero to maternal tobacco smoking (UTS) are not attributable to increases in lung compliance, resistance, or a delay in passive lung emptying. Rather, the data support the hypothesis that UTS exposure may cause a reduction in airway size as well as alterations in the growth and/or maturation of passive mechanical properties of the respiratory system in healthy newborns. © 1995 Wiley-Liss, Inc.     

Plasma volume expansion and PEEP in a canine model of acutePseudomonas pneumonia

Four groups of anesthetized, ventilated dogs (n=6 in each group) inoculated endotracheally withPseudomonas aeruginosa were studied over 5 h as bilateral, hemorrhagic pneumonia developed. Groups I and II were ventilated with zero end-expiratory pressure (ZEEP) and groups III and IV with positive end-expiratory pressure (PEEP) (8 cmH₂O). Hetastarch (6%) in saline was infused intravenously to maintain similar transmural pulmonary wedge pressures (Pw_tm) in groups I and III (approximately 5 mmHg) and groups II and IV (approximately 10 mmHg) throughout the experiment. The effects of plasma volume expansion were analyzed by comparing groups I and III with groups II and IV and of PEEP by comparing groups I and II with groups III and IV. The number of lobes with gross consolidation was greater in groups II (4.8±1.2) and IV (5±0.9) than in groups I (2±1.1) and III (3.3±1). The mean lung wet weight/body weight ratio was greater in groups II (40±11 g/kg) and IV (48±12 g/kg) than in groups I (19±3 g/kg) and III (32±6 g/kg) and in groups III and IV than in groups I and II. Plasma volume expansion, in the absence of PEEP (group II vs. group I), dramatically increased intrapulmonary shunt (Qs/Qt 5 h after inoculation: group II, 62±13%; group I, 25±12%). However, overall gas exchange 5 h after inoculation was not significantly different between PEEP-treated groups and ZEEP-treated groups despite more extensive disease in the former. Despite maintenance of Pw_tm, cardiac output fell significantly over the 5 h study period in groups III (4.3±0.7 to 3.3±1.0 L/min) and IV (7.2±1.7 to 3.8±2.4 L/min) compared to groups I (3.8±1.0 to 3.5±1.2 L/min) and II (6.9±3.2 to 7.3±2.6 L/min). We conclude that plasma volume expansion, within the normal physiological range of Pw_tm, increases the extent of pneumonia. Positive end-expiratory pressure with maintenance of Pw_tm also independently increases pneumonia size, possibly by increasing pulmonary capillary hydrostatic pressure, but masks this effect by maintaining arterial oxygenation through recruitment of additional lung units for gas exchange. The data also suggest that PEEP adversely affects cardiac performance in this model of acute pneumonia.     

Disease severity and optimum mean airway pressure level on transfer to high frequency oscillation

The aim of this study was to assess whether the severity of the infant's lung disease determined the most appropriate change in mean airway pressure (MAP) level to use on transfer from conventional ventilation to high frequency oscillation (HFO). In addition, we wished to assess whether the oscillatory frequency employed affected gas exchange. Ten premature infants with respiratory distress syndrome (RDS) were studied at a mean postnatal age of 1.5 days. During HFO, the infants were studied at a MAP equivalent of that used during conventional ventilation (baseline MAP), then at 2 and 5 cmH₂O above baseline at 10 Hz. At the MAP identified as optimum, that is, the one associated with the best oxygenation, the infants were then studied at 10, 15 and 20 Hz. Each oscillatory setting was maintained for 20 minutes after which time arterial blood gases were measured. Prior to transfer to the oscillator, the peak inspiratory pressure was recorded, the P calculated and compliance of the respiratory system C_rs) measured. In nine infants, the optimum baseline MAP was +5 cmH₂O. Oxygenation at that level was better than on conventional ventilation (P < 0.05), but there was no significant change in CO₂ elimination. The optimum MAP was related to the peak pressure during conventional ventilation (P < 0.01) and inversely related to C_rs (P < 0.01). There was no significant relationship with the P. At the optimum MAP, the only significant effect of frequency was an impairment of oxygenation at 20 Hz. We conclude that if a volume optimization strategy is pursued among infants with stiff lungs due to RDS, the appropriate starting level of MAP can be identified by stepwise changes in MAP. Impairment of oscillator performance at high frequencies can affect gas exchange. Pediatr Pulmonol. 1994; 17:178–182. © 1994 Wiley-Liss, Inc.     

Long-term pulmonary functional outcome of bronchopulmonary dysplasia and premature birth

Pulmonary function and exercise tolerance were evaluated in late childhood in two groups of prematurely born children: one group with bronchopulmonary dysplasia (BPD) [n] = 15; gestational age at birth (GA): 29.6 ± 2.8 weeks; birth weight (BW): 1,367 ± 548 g; age at test: 7.9 ± 0.6 years, and a second group without significant neonatal lung disease [pre-term (PT)] (n = 9; GA: 30.3 ± 1.7 weeks; BW: 1,440 ± 376 g; age at test: 7.8 ± 0.22 years). The results were compared with a control group of children of similar ages and heights, born at term [term born (TB)]. We observed that total lung resistance (R_L) was significantly higher in BPD (11 ± 3 cmH₂O/L/s), and in PT (9 ± 2) than in TB [5 ± 1; (P < 0.001 and P < 0.05, respectively)]. In BPD R_L was higher than in PT (P < 0.05). Dynamic lung compliance (C_LdY) was decreased in BPD (43 ± 11 mL/cmH₂O) and in PT (56 ± 17) compared with TB (76 ± 20) (P < 0.001 and P < 0.05), and also in BPD compared with PT (P < 0.05). Forced expiratory volume in 1 second (FEV₁) and FEV₁/forced vital capacity (FVC) were lower in BPD (1.07 ± 0.15 L and 72 ± 7%) than in PT (1.29 ± 0.23 L, and 80 ± 7%) (P < 0.05). Exercise tests were performed in six boys with BPD. The ratio between minute ventilation at maximal workload (V_Emax ) and the predicted value of maximal voluntary ventilation (MVV) was elevated in the six BPD boys tested, compared with five boys of Group 2 and five TB boys (87 ± 15% vs. 62 ± 14% and 65 ± 13%) (P < 0.05). We conclude that: (1) prematurity and BPD is followed by long-term airway obstruction and a mild degree of exercise intolerance and; (2) premature birth without BPD may be followed by a milder degree of airway obstruction in childhood than in infants who developed BPD during the neonatal period. Pediatr Pulmonol. 1995; 20:289–296 . © 1995 Wiley-Liss, Inc.