Treatment of type I ROP with intravitreal bevacizumab or laser photocoagulation according to retinal zone.

AIMS: To investigate the outcome of intravitreal bevacizumab (IVB) compared with laser photocoagulation in type I retinopathy of prematurity (ROP). METHODS: Case records of 54 consecutive very low birth weight (VLBW) infants with type I ROP (posterior ROP, n=33; peripheral zone II, n=21) who were treated either with IVB (n=37) or laser photocoagulation (n=17) between 2011 and 2015 were retrospectively evaluated. RESULTS: Patients with posterior ROP displayed significantly faster regression of active ROP within 12 days (range 9-15 days) if treated with IVB compared with laser photocoagulation, where active ROP regressed within 57 days (range 28-63 days) (p>0.001). No difference was observed in peripheral zone II.Five of seven patients (12%) who developed a recurrence in both eyes after IVB required additional laser photocoagulation within a mean of 12.7 weeks (11.3-15.6 weeks) after the previous treatment. After laser photocoagulation one patient with posterior ROP developed macular dragging and another patient developed a temporary exudative retinal detachment in both eyes. 12 months after treatment the spherical equivalent was not statistically significant different between IVB and laser photocoagulation in posterior ROP patients. However, IVB lead to a significant lower spherical equivalent in infants with posterior ROP (+0.37 dioptres, range -0.5 to +1.88 dioptres) compared with peripheral zone II (+3.0 dioptres range +2.0 to +4.0 dioptres, p<0.001). CONCLUSIONS: IVB leads to faster regression of active ROP in infants with posterior ROP compared with laser photocoagulation. Spherical equivalent after 12 months was comparable in those treated with IVB and laser photocoagulation, but it was significantly lower in posterior ROP than in peripheral zone II.

Effect of endotracheal tube leak on capnographic measurements in a ventilated neonatal lung model.

Uncuffed endotracheal tubes (ET) are commonly used for mechanically ventilated infants to protect airways, but this bears the risk of an air leak around the ET. In contrast to the measurements of tidal volume and respiratory mechanics, very little is known about the effect of ET leaks on capnographic measurements. To investigate the relationship between ET leakage and the CO2 measuring error of the exhaled breathing gas a neonatal lung model was used consisting of two silicon bellows. A constant but very low flow of pure CO2 was injected so that the exhaled breathing gas contained an adjustable CO2 plateau. This lung model was ventilated via a 3 mm inner diameter ET with different respiratory rates (RR) (20, 40 and 60 min(-1)). ET leaks (0-80%) were simulated by a needle valve. The end-expiratory CO2 partial pressure (PetCO2) was reduced up to zero when an air leak was simulated. Provided that the exhaled CO2 reached a plateau before entering the CO2 washout of the sample chamber by the leak flow, the magnitude of the CO2 decreased independently of RR, and only slightly with increasing ET leak. For ET leaks of up to 20% the CO2 plateau error was <10%. However, in newborns with stiff lungs and a short alveolar plateau capnographic measurements should be interpreted with caution if the ET leak is considerable.

Leak during manual neonatal ventilation and its effect on the delivered pressures and volumes: an in vitro study.

BACKGROUND: Mask leak is a frequent problem during manual ventilation. Our aim was to investigate the effect of predefined leaks on delivered peak inflation pressure (PIP), positive end-expiratory pressure (PEEP) and tidal volume (V(t)) when using different neonatal manual ventilation devices. METHODS: A neonatal-lung model was ventilated at different respiratory rates (RRs, 40, 60, 80/min) using a mechanically operated self-inflating bag (SIB) and a manually operated T-piece resuscitator (PIP = 20 cm H(2)O, PEEP = 5 cm H(2)O). Four open tubes of different lengths, which produced up to 90% leak, were consecutively attached between the ventilation device and the lung model. A pneumotachograph was used to measure pressures, flow and volume. RESULTS: With increasing leak (0-90%) PIP and PEEP decreased significantly (p < 0.001) for both devices. Using the SIB, the mean ± SD PIP fell from 20.1 ± 0.3 to 15.9 ± 7 cm H(2)O and PEEP fell from 5.0 ± 0 to 0.3 ± 0.5 cm H(2)O, leading to an increased pressure difference (Δp); V(t) increased from 8.8 ± 0.7 to 11.1 ± 0.8 ml (p < 0.001). With increasing RRs, the leak-dependent changes were significantly lower (p < 0.001). Using the T-piece resuscitator, PIP dropped independent of RRs from 20.3 ± 0.5 to 18.5 ± 0.6 cm H(2)O and PEEP from 5.1 ± 0.4 to 4.0 ± 0 cm H(2)O, while Δp and V(t) did not differ significantly. CONCLUSION: The decrease in PIP and PEEP with increasing leak is RR dependent and distinctly higher when using an SIB compared to a T-piece device. In contrast to V(t) delivered with the SIB, V(t) delivered by the T-piece resuscitator was nearly constant even for leaks up to 90%.

Adverse cardiorespiratory events following primary vaccination of very low birth weight infants.

OBJECTIVE: To examine the relationship between primary vaccination of preterm infants and prevalence ratios of associated factors for unwanted cardiorespiratory events, following the recommendation of the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices for immunization of preterm infants at 2 months of chronological age. METHODS: Two-year retrospective study of very low birth weight infants receiving their primary vaccination. Major cardiorespiratory events, such as apnea, bradycardia, SpO(2) desaturation, and minor adverse events, such as temperature instability, poor handling and local reactions, were recorded. Prevalence ratio with 95% confidence interval for associated factors between infants with and without cardiorespiratory events was calculated. RESULTS: Eighty neonates were studied (median [range] birth weight 970 g [428-1,490]), gestational age of 27.4 weeks (23.3-33). Adverse reactions occurred in 35 (44%): minor events in 19 (24%) patients, major events in 28 (35%). Infants with major events had significantly lower gestational age (p = 0.008) and a higher incidence of bronchopulmonary dysplasia (71% vs. 48%; p < 0.05). In very low birth weight infants with major events, O(2) desaturations before vaccination were 3.40 (1.41-8.23) times higher and treatment with methylxanthines for apnea and bradycardia syndrome was 8.05 (2.50-25.89) times higher compared to infants without major events. CONCLUSION: Major cardiorespiratory events occurred in over 1/3 of all very low birth weight infants after vaccination. Associated factors were low gestational age, bronchopulmonary dysplasia, methylxanthine treatment, and persisting O(2) desaturations before vaccination. Primary vaccination of very low birth weight infants should be performed under continuous monitoring of vital parameters.

Eventos cardiorrespiratórios adversos após vacinação primária de recém-nascidos de muito baixo peso / Adverse cardiorespiratory events following primary vaccination of very low birth weight infants

OBJETIVO: Examinar a relação entre vacinação primária de recém-nascidos pré-termo e razões de prevalência de fatores associados a eventos cardiorrespiratórios indesejados, seguindo recomendações do Comitê Consultivo de Práticas de Imunização do Centers for Disease Control and Prevention para imunização de recém-nascidos pré-termo aos 2 meses de idade cronológica. MÉTODOS: Estudo retrospectivo de 2 anos de recém-nascidos de muito baixo peso que receberam vacinação primária. Foram registrados eventos cardiorrespiratórios maiores, como apneia, bradicardia, dessaturação de SpO2, e eventos menores, como instabilidade de temperatura, comportamento inapropriado e reações locais. Foi calculada a razão de prevalência com intervalo de confiança de 95% para fatores associados entre recém-nascidos com e sem eventos cardiorrespiratórios. RESULTADOS: Foram estudados 80 recém-nascidos (mediana de peso ao nascer [:intervalo]: de 970 g [:428-1.490]:), idade gestacional de 27,4 semanas (23,3-33). Ocorreram reações adversas em 35 (44%): eventos menores em 19 (24%) pacientes, eventos maiores em 28 (35%). Recém-nascidos com eventos maiores tiveram idade gestacional significativamente menor (p = 0,008) e incidência mais alta de displasia broncopulmonar (71% versus 48%; p < 0,05). Em recém-nascidos de muito baixo peso com eventos maiores, o número de casos de dessaturação de O2 antes da vacinação foi 3,40 (1,41-8,23) vezes maior, e o tratamento com metilxantina para síndrome de apneia e bradicardia foi 8,05 (2,50-25,89) vezes maior em comparação com recém-nascidos sem eventos maiores. CONCLUSÃO: Eventos cardiorrespiratórios maiores ocorreram em mais de 1/3 de todos os recém-nascidos de muito baixo peso após a vacinação. Os fatores associados foram baixa idade gestacional, displasia broncopulmonar, tratamento com metilxantina e dessaturação de O2 persistente antes da vacinação. A vacinação primária de recém-nascidos de muito baixo peso deve ser realizada sob monitoramento contínuo de parâmetros vitais.

OBJECTIVE: To examine the relationship between primary vaccination of preterm infants and prevalence ratios of associated factors for unwanted cardiorespiratory events, following the recommendation of the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices for immunization of preterm infants at 2 months of chronological age. METHODS: Two-year retrospective study of very low birth weight infants receiving their primary vaccination. Major cardiorespiratory events, such as apnea, bradycardia, SpO2 desaturation, and minor adverse events, such as temperature instability, poor handling and local reactions, were recorded. Prevalence ratio with 95% confidence interval for associated factors between infants with and without cardiorespiratory events was calculated. RESULTS: Eighty neonates were studied (median [:range]: birth weight 970 g [:428-1,490]:), gestational age of 27.4 weeks (23.3-33). Adverse reactions occurred in 35 (44%): minor events in 19 (24%) patients, major events in 28 (35%). Infants with major events had significantly lower gestational age (p = 0.008) and a higher incidence of bronchopulmonary dysplasia (71% vs. 48%; p < 0.05). In very low birth weight infants with major events, O2 desaturations before vaccination were 3.40 (1.41-8.23) times higher and treatment with methylxanthines for apnea and bradycardia syndrome was 8.05 (2.50-25.89) times higher compared to infants without major events. CONCLUSION: Major cardiorespiratory events occurred in over 1/3 of all very low birth weight infants after vaccination. Associated factors were low gestational age, bronchopulmonary dysplasia, methylxanthine treatment, and persisting O2 desaturations before vaccination. Primary vaccination of very low birth weight infants should be performed under continuous monitoring of vital parameters.

Positive effects of early continuous positive airway pressure on pulmonary function in extremely premature infants: results of a subgroup analysis of the COIN trial.

OBJECTIVE: Early continuous positive airway pressure (CPAP) may reduce lung injury in preterm infants. PATIENTS AND METHODS: Spontaneously breathing preterm infants were randomised immediately after birth to nasal CPAP or intubation, surfactant treatment and mechanical ventilation. Pulmonary function tests approximately 8 weeks post-term determined tidal breathing parameters, respiratory mechanics and functional residual capacity (FRC). RESULTS: Seventeen infants received CPAP and 22 mechanical ventilation. Infants with early CPAP had less mechanical ventilation (4 vs 7.5 days; p=0.004) and less total respiratory support (30 vs 47 days; p=0.017). Post-term the CPAP group had lower respiratory rate (41 vs 48/min; p=0.007), lower minute ventilation (223 vs 265 ml/min/kg; p=0.009), better respiratory compliance (0.99 vs 0.82 ml/cm H(2)O/kg; p=0.008) and improved elastic work of breathing (p=0.004). No differences in FRC were found. CONCLUSIONS: Early CPAP is feasible, shortens the duration of respiratory support and results in improved lung mechanics and decreased work of breathing.

Delivery room management of very low birth weight infants in Germany, Austria and Switzerland--a comparison of protocols.

BACKGROUND: Surveys from the USA, Australia and Spain have shown significant inter-institutional variation in delivery room (DR) management of very low birth weight infants (VLBWI, <1500g) at birth, despite regularly updated international guidelines. OBJECTIVE: To investigate protocols for DR management of VLBWI in Germany, Austria and Switzerland and to compare these with the 2005 ILCOR guidelines. METHODS: DR management protocols were surveyed in a prospective, questionnaire-based survey in 2008. Results were compared between countries and between academic and non-academic units. Protocols were compared to the 2005 ILCOR guidelines. RESULTS: In total, 190/249 units (76%) replied. Protocols for DR management existed in 94% of units. Statistically significant differences between countries were found regarding provision of 24 hr in house neonatal service; presence of a designated resuscitation area; devices for respiratory support; use of pressure-controlled manual ventilation devices; volume control by respirator; and dosage of Surfactant. There were no statistically significant differences regarding application and monitoring of supplementary oxygen, or targeted saturation levels, or for the use of sustained inflations. Comparison of academic and non-academic hospitals showed no significant differences, apart from the targeted saturation levels (SpO2) at 10 min. of life. Comparison with ILCOR guidelines showed good adherence to the 2005 recommendations. SUMMARY: Delivery room management in German, Austrian and Swiss neonatal units was commonly based on written protocols. Only minor differences were found regarding the DR setup, devices used and the targeted ranges for SpO2 and FiO2. DR management was in good accordance with 2005 ILCOR guidelines, some units already incorporated evidence beyond the ILCOR statement into their routine practice.

The effect of surgery on lung volume and conventional monitoring parameters in ventilated newborn infants.

In newborn infants, thoraco-abdominal surgery is a serious intervention with respect to gas exchange and lung mechanics. This prospective clinical study compared surgery-induced changes in functional residual capacity (FRC) and ventilation inhomogeneity (VI) indices with changes in conventional monitoring parameters. Of 29 ventilated newborns (mean weight 2,770+/-864 g at surgery), 13, nine and seven underwent thoracic, abdominal or congenital diaphragmatic hernia (CDH) surgery, respectively. The multiple breath washout (MBWO) technique using heptafluoropropane as tracer gas (Babylog 8000; Dräger, Lübeck, Germany) was performed <6 h before surgery, 22-24 h after surgery and <6 h before extubation. Gas exchange, respiratory mechanics, FRC and VI index data were recorded. Thoraco-abdominal surgery resulted in changes to FRC and VI indices in a procedure-specific manner; however, these changes were not reflected in conventional mechanical or ventilatory monitoring parameters. FRC decreased in non-CDH infants, while FRC increased and VI indices decreased in CDH infants. Despite improvements, the differences in FRC and VI between CDH and non-CDH infants indicated persistent impaired lung function in CHD infants. MBWO can be advantageously used to measure the effect of surgery on the lung. While FRC and VI indices changed following surgery, conventional monitoring parameters did not.

Reliability of two common PEEP-generating devices used in neonatal resuscitation.

BACKGROUND: Approximately 15% of neonates require respiratory support at birth, the demand of which increases with decreasing gestational age. Positive end-expiratory pressure (PEEP) stabilizes the airways and improves both pulmonary functional residual capacity and compliance. Self-inflating bags, which can be used with and without a PEEP-valve, are most commonly used for neonatal resuscitation, pressure limited T-piece resuscitators are becoming increasingly popular. The aim of the study was to investigate the reliability of PEEP provision of both systems. MATERIAL AND METHODS: An intubated, leak free mannequin (equivalent to 1 kg neonate, pulmonary compliance 0.2 ml*cmH (2)O (-1)) was used for testing both devices. Eleven PEEP-valves attached to a 240 ml self-inflating bag and 5 T-piece resuscitators were investigated. Provision of a PEEP of 5 cmH (2)O (gas flow of 8l/min) at manual ventilation at breaths 40/min was investigated. Data were recorded using a standard pneumotachograph. RESULTS: Only 1/11 PEEP-valves provided a PEEP of 5 cmH (2)O (mean (SD) 2.95 (1.82) cmH (2)O, CV 0.62%), in 5/11 (45%) PEEP was <3 cmH (2)O, in 2 of the PEEP-valves produced a PEEP below 0.3 cmH (2)O. All T-piece resuscitators provided a PEEP >5 cmH (2)O (mean 5.59 (0.32) cmH (2)O, CV 0.06%). Significant differences in individual performance per device (p<0.05) and between systems (p=0.007) were found. CONCLUSION: Self-inflating bags did not reliably provide the desired PEEP of 5 cmH (2)O, whereas T-piece resuscitators did reliably provide the set PEEP-level, with less variability. When using self-inflating bags with PEEP-valves, neonatologists should check the equipment regarding the reliability of PEEP provision.

Relationship between endotracheal tube leakage and under-reading of tidal volume in neonatal ventilators.

AIM: Protective ventilation in neonates requires careful volume monitoring to prevent ventilator-induced lung injury caused by baro/volutrauma and hence chronic lung disease. This study investigated the effect of endotracheal tube (ET) leakage on the displayed tidal volume using an in vitro model. METHODS: A neonatal lung model was ventilated via a 3 mm ET using three ventilators [Babylog 8000 (BL), Leoni (LE) and Stephanie (ST)]. Tidal volume was measured by each ventilator at the Y-piece and by a pneumotach (CO(2)SMO(+)) in the model. ET leaks were simulated by open tubes of different lengths. PIP (20 cmH(2)O) and PEEP (5 cmH(2)O) were kept constant, and the respiratory rate (RR) was varied between 20/min and 70/min (Ti:Te = 1:1). RESULTS: Tidal volume displayed by a ventilator decreased independently of RR with increasing leakage up to 21% (BL), 30% (LE) and 33% (ST). However, the volume delivered to the lung was nearly constant. The displayed leakage varied between 0 and 78% and was dependent on RR and leakage resistance. There were distinct differences between the three ventilators in the relationship between displayed leakage and volume error. Accepting a volume error <10% for RR between 20 and 70/min, ET leakage of up to 20% for BL, 12% for LE, but only <5% for ST, was acceptable. CONCLUSION: Tidal volume underestimation arising from ET leakage depends on ventilator pressures, timing parameters and ventilator-specific algorithms for signal processing. Therefore, neonatologists should be aware of these issues to prevent lung over-inflation when adjusting target volume in the presence of ET leakage.

Comparison of different techniques to measure air leaks during CPAP treatment in neonates.

UNLABELLED: Continuous positive airway pressure (CPAP) is routinely used for respiratory support in neonates. Air leaks are not uncommon and can hinder treatment. This study compared leak flow data obtained using different leak definitions through modeling and in vitro measurements. METHODS: Using a computer simulation of an ideal CPAP system, the relationship between leak flow and three leak definitions was investigated. The leak flow was based on the measured inspiratory, expiratory and averaged breathing flow as commonly used in neonates. The theoretical results were compared with in vitro measurements using a commercial CPAP device for neonates (Leoni, Heinen & Löwenstein, Germany). Spontaneous breathing was simulated using a mechanical lung model, and defined air leaks were simulated using open silicone tubes of different lengths. RESULTS: Computer simulations showed that leak calculations were affected by leak flow and breathing pattern, and that the relationships were mostly non-linear. There were large differences in the results between the three leak definitions. The in vitro measurements correlated strongly with the theoretical modeling results. The derived numerical volume correction reduced the leak-dependent volume error in the mean (S.D.) to -1.6 (4.6)%. CONCLUSION: It is difficult to compare different measuring conditions and different CPAP devices due to the variation in results depending on the leak definition and the breathing pattern. Leak flow displays would provide superior air leak monitoring.

Assessment of volume and leak measurements during CPAP using a neonatal lung model.

Although several commercial devices are available which allow tidal volume and air leak monitoring during continuous positive airway pressure (CPAP) in neonates, little is known about their measurement accuracy and about the influence of air leaks on volume measurement. The aim of this in vitro study was the validation of volume and leak measurement under CPAP using a commercial ventilatory device, taking into consideration the clinical conditions in neonatology. The measurement accuracy of the Leoni ventilator (Heinen & Löwenstein, Germany) was investigated both in a leak-free system and with leaks simulated using calibration syringes (2-10 ml, 20-100 ml) and a mechanical lung model. Open tubes of variable lengths were connected for leak simulation. Leak flow was measured with the flow-through technique. In a leak-free system the mean relative volume error +/-SD was 3.5 +/- 2.6% (2-10 ml) and 5.9 +/- 0.7% (20-60 ml), respectively. The influence of CPAP level, driving flow, respiratory rate and humidification of the breathing gas on the volume error was negligible. However, an increasing F(i)O(2) caused the measured tidal volume to increase by up to 25% (F(i)O(2) = 1.0). The relative error +/- SD of the leak measurements was -0.2 +/- 11.9%. For leaks > 19%, measured tidal volume was underestimated by more than 10%. In conclusion, the present in vitro study showed that the Leoni allowed accurate volume monitoring under CPAP conditions similar to neonates. Air leaks of up to 90% of patient flow were reliably detected. For an F(i)O(2) > 0.4 and for leaks > 19%, a numerical correction of the displayed volume should be performed.

Use of continuous positive airway pressure (CPAP) in neonatal units--a survey of current preferences and practice in Germany.

UNLABELLED: There is only limited evidence regarding the equipment or the settings (pressure and flow) at which CPAP should be applied in neonatal care. Aims of this nationwide survey of German neonatal units were to investigate (1) for which clinical indications CPAP was employed, (2) which CPAP equipment was used, (3) which CPAP settings were applied. A questionnaire on the use of CPAP was sent to all children's hospitals in Germany. Data were stratified and compared by level of medical care provided (non-academic children's hospital, academic teaching hospital and university children's hospital). 274 institutions were contacted by mailed questionnaire. The response rate was 86%, 90 non-academic children's hospitals, 119 academic teaching hospitals and 26 university children's hospitals replied. (1) There were no statistically significant difference in CPAP use between the institutions: 231 (98%) used CPAP for treating respiratory distress syndrome, 225 (96%) for treating apnoea-bradycardia-syndrome and 230 (98%) following extubation. (2) Commercial CPAP systems were employed by 71% of units, the others used a combination of different devices. Respirator generated CPAP was most commonly used. Exclusively mononasal CPAP was used by only 9%, and binasal CPAP by 55% of institutions. (3) Median CPAP was 4.5 cm H2O (range 3-7), median maximum CPAP was 7 cm H2O (range 4-10), with no statistically significant differences between the hospitals. CONCLUSION: Between units, CPAP was given via a broad range of CPAP systems and at varying pressure settings. The reported differences reflects personal experiences and preferences, rather than sound evidence from clinical trials.

The effect of changing ventilator settings on indices of ventilation inhomogeneity in small ventilated lungs.

BACKGROUND: In ventilated newborns the use of multiple breath washout (MBW) techniques for measuring both lung volume and ventilation inhomogeneity (VI) is hampered by the comparatively high dead space fraction. We studied how changes in ventilator settings affected VI indices in this particular population. METHODS: Using a computer simulation of a uniformly ventilated volume the interaction between VI indices (lung clearance index (LCI), moment ratios (M1/M0, M2/M0, AMDN1, AMDN2) of the washout curve) and tidal volume (VT), dead space (VD) and functional residual capacity (FRC) were calculated. The theoretical results were compared with measurements in 15 ventilated piglets (age <12 h, median weight 1135 g) by increasing the peak inspiratory pressure (PIP). FRC and VI indices were measured by MBW using 0.8% heptafluoropropane as tracer gas. RESULTS: The computer simulation showed that the sensitivity of most VI indices to changes in VD/VT and VT/FRC increase, in particular for VD/VT > 0.5. In piglets, the raised PIP caused a significant increase of VT from 15.4 +/- 9.5 to 21.9 +/- 14.7 (p = 0.003) and of the FRC from 31.6 +/- 14.7 mL to 35.0 +/- 15.9 mL (p = 0.006), whereas LCI (9.15 +/- 0.75 to 8.55 +/- 0.74, p = 0.019) and the moment ratios M1/M0, M2/M0 (p < 0.02) decreased significantly. No significant changes were seen in AMDN1 and AMDN2. The within-subject variability of the VI indices (coefficient of variation in brackets) was distinctly higher (LCI (9.8%), M1/M0 (6.6%), M2/M0 (14.6%), AMDN1 (9.1%), AMDN2 (16.3%)) compared to FRC measurements (5.6%). Computer simulations showed that significant changes in VI indices were exclusively caused by changes in VT and FRC and not by an improvement of the homogeneity of alveolar ventilation. CONCLUSION: In small ventilated lungs with a high dead space fraction, indices of VI may be misinterpreted if the changes in ventilator settings are not considered. Computer simulations can help to prevent this misinterpretation.

Differences in tidal breathing between infants with chronic lung diseases and healthy controls.

BACKGROUND: The diagnostic value of tidal breathing (TB) measurements in infants is controversially discussed. The aim of this study was to investigate to what extent the breathing pattern of sleeping infants with chronic lung diseases (CLD) differ from healthy controls with the same postconceptional age and to assess the predictive value of TB parameters. METHODS: In the age of 36-42 postconceptional weeks TB measurements were performed in 48 healthy newborns (median age and weight 7d, 3100 g) and 48 infants with CLD (80d, 2465 g)) using the deadspace-free flow-through technique. Once the infants had adapted to the mask and were sleeping quietly and breathing regularly, 20-60 breathing cycles were evaluated. Beside the shape of the tidal breathing flow-volume loop (TBFVL) 18 TB parameters were analyzed using ANOVA with Bonferroni correction. Receiver-operator characteristic (ROC) curves were calculated to investigate the discriminative ability of TB parameters. RESULTS: The incidence of concave expiratory limbs in CLD infants was 31% and significantly higher compared to controls (2%) (p < 0.001). Significant differences between CLD infants and controls were found in 11/18 TB parameters. The largest differences were seen in the mean (SD) inspiratory time 0.45(0.11)s vs. 0.65(0.14)s (p < 0.0001) and respiratory rate (RR) 55.4(14.2)/min vs. 39.2(8.6)/min (p < 0.0001) without statistically significant difference in the discriminative power between both time parameters. Most flow parameters were strongly correlated with RR so that there is no additional diagnostic value. No significant differences were found in the tidal volume and commonly used TB parameters describing the expiratory flow profile. CONCLUSION: The breathing pattern of CLD infants differs significantly from that of healthy controls. Concave TBFVL and an increased RR measured during quiet sleep and under standardized conditions may indicate diminished respiratory functions in CLD infants whereas most of the commonly used TB parameters are poorly predictive.

Breathing gas perfluorocarbon measurements using an absorber filled with zeolites.

BACKGROUND: Perfluorocarbon (PFC) has been widely used in the treatment of respiratory diseases; however, PFC content of the breathing gases remains unknown. Therefore, we developed an absorber using PFC selective zeolites for PFC measurement in gases and investigated its accuracy. METHODS: To generate a breathing gas with different PFC contents a heated flask was rinsed with a constant air flow of 4 litre x min(-1) and 1, 5, 10, and 20 ml of PFC were infused over 20 min using an infusor. The absorber was placed on an electronic scale and the total PFC volume was calculated from the weight gain. RESULTS: Steady-state increase in weight was achieved 3.5 min after stopping the infusion. The calculated PFC volume was slightly underestimated but the measuring error did not exceed -1% for PFC less than 1 ml. The measurement error decreased with increasing PFC volume. CONCLUSIONS: This zeolite absorber is an accurate method to quantitatively determine PFC in breathing gases and can be used as a reference method to validate other PFC sensors.

In vitro assessment of equipment and software to assess tidal breathing parameters in infants.

The aim of this in vitro study was to compare the measurement accuracy of two currently available devices for measuring tidal breathing in infants. A mechanical model pump was used to generate flow profiles which simulated those observed in infants. A range of flows was applied simultaneously to two different devices, namely the commercially available SensorMedics 2600 (SM 2600) and more recently developed, custom-made equipment based on the flow-through technique (FTT). Automatically derived values from both devices were compared with one another and with manual calculations of printouts of the same breaths. There were no differences in the raw flow signal obtained from the two devices, nor between values calculated automatically or manually from the FTT. Similarly, the deviations between the FTT and SM 2600 were <3% for tidal volume, respiratory frequency and minute ventilation. However, when comparing either with manually calculated values or those derived automatically from the FTT, there was a systematic and highly significant underestimation of shape-dependent parameters, such as the time to peak tidal expiratory flow as a proportion of tidal expiratory time (tPTEF/tE), derived by the SM 2600. The lower the applied flow, the higher the observed deviations, the underestimation being up to 60% when flows simulating those observed in preterm neonates were applied. These errors appear to result from differences in signal processing such as the algorithms used for breath detection and can only be detected if appropriate nonsinusoidal flow profiles representing those seen in infants are used to evaluate equipment.

Effect of apparatus dead space on breathing parameters in newborns: "flow-through" versus conventional techniques.

Commercial devices for tidal breathing measurements in newborns allow only short-term measurements, due to the high apparatus dead space of the face mask and pneumotachometer. The flow-through technique (FTT) minimizes the dead space by a background flow, thereby allowing long-term measurements. The aim of this study was to investigate the comparability of tidal breathing parameters using both techniques. Paired measurements of tidal breathing were performed in 86 sleeping infants (median (range) body weight 2.8 kg (1.9-5.3 kg), age 65 days (3-150 days)), using the FTT and SensorMedics 2600 (SM 2600). There was a significant bias (p <0.001) in all tidal breathing parameters. Compared with the FTT, increases (95% confidence interval (CI)) in tidal volume (VT), respiratory frequency (fR), and minute ventilation (V'E) were 0.74 (0.5-1.0) mL.kg(-1), 9.0 (6.9-11.2).min(-1) and 92 (74-109) mL.min(-1).kg(-1) when measured with the SM 2600, representing average increases of 13, 17 and 30%, respectively, in response to the added dead space. By contrast, time to peak tidal expiratory flow as a proportion of expiratory time (tPTEF/tE) was changed by -0.09 (-0.11-0.08). The mean (95% CI) change in tPTEF/tE of -54 (-62-45)%, when measured in infants by the SM 2600, was remarkably similar to that observed during in vitro validation studies (-59 (-73-44)%), suggesting that the discrepancies in timing parameters may be largely attributable to differences in signal processing. In conclusion, differences in measurement technique and precision of the devices used can result in significant differences in tidal breathing parameters. This may impede the comparison of results within and between infants and the clinical interpretation of tidal breathing measurements in newborns.

Deadspace free ventilatory measurements in newborns during mechanical ventilation.

OBJECTIVE: To improve the accuracy of ventilatory measurements in ventilated newborns by means of a numerical correction when a deadspace free differential measuring method using two pneumotachographs (PNTs) is applied and to investigate the clinical usefulness of this correction procedure. DESIGN: In vitro study and prospective animal study. SETTING: Research laboratory of the Clinic of Neonatology and the Animal Research Laboratory, Charité Hospital Berlin. SUBJECTS: Ten newborn piglets, weighing 610-1340 g (median, 930 g), age <12 hrs. INTERVENTIONS: The accuracy of both the deadspace free method and the endotracheal flow measurements (conventional method) was investigated using mechanical lung models. A correction procedure for the deadspace free method was developed considering signal delay time and tube compliance between both PNTs. This method was applied to the piglets measured during partial liquid ventilation (PLV). Measurements were done before and after lung lavage and during 30 and 120 mins of PLV (30 mL/kg body weight perfluorocarbon). MEASUREMENTS AND MAIN RESULTS: In vitro measurements showed volume differences between both methods of 8%, 12%, 16%, and 17%, respectively, depending on the distance between the PNTs of 10, 60, 120, and 180 cm. After applying the correction algorithm, the differences decreased to 3%, 0%, -2%, and -8%, respectively. The piglets were measured with 120-cm tube length between the PNTs. The correction algorithm reduced the measured tidal volume before lavage by 7%, after lavage by 14%, 30-min PLV by 12%, and 120-min PLV by 10%, corresponding to the changes in respiratory compliance of 1.2, 0.6, 1.0, and 1.1 mL/cm H2O. CONCLUSIONS: The deadspace free method can be advantageously used for continuous measurements in newborns despite much higher technical expense. The correcting procedure improved the accuracy of the volume measurement remarkably, especially for lower respiratory compliance.