Cathy Worwa

Observational Study of Humidified High-Flow Nasal Cannula Compared with Nasal Continuous Positive Airway Pressure

OBJECTIVES To conduct an in vitro evaluation of a humidified high-flow nasal cannula (HFNC) system at different flows, cannula sizes, and air leaks and also an in vivo analysis of mean end-expiratory esophageal pressure (EEEP) from nasal continuous positive airway pressure at 6 cm H(2)O (NCPAP+6) versus HFNC. STUDY DESIGN In the in vitro study, we measured HFNC system pressure and flow, with varying degrees of leak and with and without the use of a pressure-limiting valve. In the in vivo study, we measured EEEP in 15 newborns on NCPAP+6 and then on HFNC at 6 L/minute, with flow decreased by 1 L/minute every 30 minutes. Heart rate, respiratory rate, fraction of inspired oxygen, arterial oxygen saturation, respiratory distress syndrome score, and EEEP were recorded for each intervention. Data analysis was done using repeated-measures analysis of variance and linear regression. RESULTS In the in vitro study, in the absence of leaks, the pressures were limited by the pressure-limiting valve only at flows > or = 2 L/minute. With leaks of 30% and 50%, delivered pressures were always < 3 cm H(2)O. In the in vivo study, respiratory rate increased from baseline (NCPAP+6) as flow decreased (P < .02). Intrapatient and interpatient coefficients of variation were always high. CONCLUSIONS A pressure-limiting valve is necessary in a HFNC system. Although mean EEEP levels were similar in NCPAP+6 and HFNC, tachypnea developed as flow diminished. This system apparently cannot predict EEEP, because of interpatient and intrapatient variation.

Gas exchange and lung inflammation using nasal intermittent positive-pressure ventilation versus synchronized intermittent mandatory ventilation in piglets with saline lavage-induced lung injury: an observational study.

Objective:Physiologic and pathologic comparison of two modes of assisted ventilation, nasal intermittent positive-pressure ventilation (NIPPV) and synchronized intermittent mandatory ventilation (SIMV), in spontaneously breathing term newborn piglets with saline lavage-induced lung injury. Design:After inducing acute lung injury via repetitive saline lavage, piglets were randomized to NIPPV (n = 12) or SIMV (n = 11) and treated for 6 hrs. Setting:Clinical laboratory. Subjects:Spontaneously breathing term newborn piglets. Interventions:Invasive (SIMV) or noninvasive (NIPPV) assisted ventilation for 6 hrs. Measurements:Physiologic parameters and arterial blood gases were continuously monitored. At the conclusion of the study, lung tissue was obtained to analyze for evidence of inflammation, including myeloperoxidase, interleukin-8, and hydrogen peroxide levels, as well as for evidence of pathologic injury. Main Results:Piglets treated with NIPPV demonstrated higher arterial blood gas pH (p < .001), lower Paco2 (p < .05), and a lower set respiratory rate (p < .0001) as compared with the SIMV-treated piglets. The piglets in the SIMV group had higher Pao2/Pao2 ratio than those in the NIPPV group (p = .001). There was significantly more interstitial inflammation (p = .04) in the SIMV-treated piglets compared with the NIPPV-treated piglets. Total respiratory rate, heart rate, blood pressure, oxygen saturation, and biochemical markers of lung inflammation were not different between the groups. Conclusion:In surfactant-deficient term newborn piglets, NIPPV offers an effective and noninvasive ventilatory strategy with the potential for less pathologic lung inflammation.

Laryngeal Mask Airway for Surfactant Administration in a Newborn Animal Model

Premature infants are subjected to adverse effects of intubation to benefit from surfactant. We hypothesized that administration of surfactant through a laryngeal mask airway (LMA) is as effective as administration through an endotracheal tube (ETT) and that time and physiologic changes during instrumentation will be less in the LMA group. This study is a randomized, controlled trial using newborn pigs. Lung injury was induced via surfactant washout. Animals were randomized into groups: 1) LMA placed, no surfactant administered (control; n = 8); 2) surfactant via an LMA (LMA group; n = 8); and 3) surfactant via an ETT (ETT group; n = 8). We demonstrated that partial pressure of oxygen in arterial blood (Pao2) levels of the LMA and ETT groups were not statistically different. Time for successful placement of LMA was 19 ± 1 s versus ETT 123 ± 35 s (mean ± SEM); number of attempts for successful LMA placement was 1.1 (1–2) versus ETT 1.9 (1–7) [mean (range)]. Administration of surfactant via an LMA compared with an ETT resulted in similar improvements in oxygenation. Placement of the device required less time and fewer attempts. These data suggest that further study in human neonates is justified. If proven effective, some infants with respiratory distress may be able to receive surfactant while avoiding intubation.

Aerosolized KL4 surfactant improves short-term survival and gas exchange in spontaneously breathing newborn pigs with hydrochloric acid-induced acute lung injury.

Surfactant therapy may be beneficial in acute lung injury (ALI). In spontaneously breathing newborn pigs with ALI supported with continuous positive airway pressure (CPAP), we evaluated the hypothesis that aerosolized KL4 surfactant (AERO KL4S) would provide a similar therapeutic effect as intratracheal KL4 surfactant (ETT KL4S) when compared to controls.

Decreased Lung Injury after Surfactant in Piglets Treated with Continuous Positive Airway Pressure or Synchronized Intermittent Mandatory Ventilation

Background: Treatment with surfactant (S) decreases lung injury in paralyzed, mechanically ventilated animals. The use of nasal continuous positive airway pressure (CPAP) as an alternative to mechanical ventilation may further improve acute pulmonary outcomes. Objectives: To evaluate the effect of surfactant (+S, –S) and synchronized intermittent mandatory ventilation (SIMV) on lung morphology and inflammatory markers in 24 spontaneously breathing piglets treated with CPAP or SIMV after saline lavage-induced lung injury. Methods: After induction of lung injury, animals were randomized to CPAP–S, CPAP+S or SIMV+S and treated for 4 h. Physiologic parameters were continuously monitored. After treatment, animals were euthanized and lungs fixed. Bronchoalveolar lavage (BAL) samples were collected for neutrophil count and H2O2. Results: No physiologic differences were noted. BAL fluid from CPAP–S animals contained more neutrophils and more neutrophil H2O2 than fluid from the SIMV+S or CPAP+S groups (p < 0.05 or greater). Pathologic injury scores were higher in dependent lung regions from CPAP groups (p < 0.05). Injury pattern scores showed greater dependent alveolar inflammation in all (p < 0.02), with more dependent atelectasis in the CPAP groups (p < 0.01). Morphometrics showed less total open alveolar air space in nondependent regions of the SIMV+S group compared to CPAP groups (p < 0.001). Dependent regions showed less total open alveolar air space compared to nondependent regions in the CPAP groups (p < 0.001). Conclusions: Animals treated with surfactant prior to CPAP or SIMV had less acute lung injury. SIMV+S animals had less open air space in nondependent regions. This suggests, during early ventilatory support, surfactant administration may modulate pulmonary inflammation. CPAP alone without surfactant may not provide optimal pulmonary protection. The addition of mechanical breaths may alter and add to injury.

Improved gas exchange and survival after KL-4 surfactant in newborn pigs with severe acute lung injury

To determine the effectiveness of artificial surfactant therapy using KL‐4 surfactant in newborn pigs with hydrochloric acid (HCl)‐induced acute lung injury (ALI).

Bi-level CPAP does not improve gas exchange when compared with conventional CPAP for the treatment of neonates recovering from respiratory distress syndrome

Lampland AL, Plumm B, Worwa C, et al. Bi-level CPAP does not improve gas exchange when compared with conventional CPAP for the treatment of neonates recovering from respiratory distress syndrome. This paper was incorrectly published on the Online First page of Archives of Disease in Childhood, it should have been published on the Online First page for ADC Fetal & Neonatal Edition. We apologise to the author for this error, the paper has now been moved to the correct edition.

42 DEVELOPMENT OF MATERNAL AND PATERNAL VOICE RECOGNITION MEMORY IN NEWBORN INFANTS.

Objective Further understanding of memory development in newborn infants is important because brain structures critical for memory are vulnerable to perinatal injury. Although newborns can recognize their mothers9 voices, there is a high degree of prenatal and postnatal experience, and it is not clear whether lesser degrees of experience will result in memory formation. Our purpose was to further evaluate the role of experience in neonatal auditory recognition memory by comparing how newborns respond to the mother9s voice (high degree of experience) or the father9s voice (less experience) versus a stranger9s voice using event-related potentials (ERPs), a technique commonly used in cognitive neuroscience. Methods Subjects (N = 30) were healthy, term newborns ≤ 4 days of age. ERPs were recorded from 16 standard scalp electrodes during active sleep while listening to recordings of the word “baby” in the mother9s voice alternating with a female stranger9s voice or father9s voice alternating with a male stranger9s voice. Results Of the 15 mothers, 80% spoke specifically to the fetus in utero on a daily basis and all spoke frequently to the infant after birth. Of the 15 fathers, 66% reported talking specifically to the fetus daily (33%) or weekly (33%). Postnatally, 73% of the fathers spent 12 to 24 hours per day rooming-in and 93% spoke frequently to the baby. Infants9 ERPs demonstrated recognition of both mothers9 and fathers9 voices, evidenced by increased negativity to the stranger9s voice from 400 to 1200 msec over the midline frontal electrode (Fz) (mean amplitude for parent9s voice: 2.2 ± 1.8 μv; stranger9s voice: −2.0 ± 1.3 μv; p = .0216), with similar amplitudes for fathers9 and mothers9 voices. There was a significant difference between male and female voices over the right hemisphere, most notable over the posterior right temporal area (T6) from 1,200 to 2,000 msec, with amplitudes for male voices (father and stranger, 1.4 ± 1.4 μv) significantly greater than those elicited by female voices (mother and stranger, −2.0 ± 1.1 μv; p = .045). Conclusion Although pre- and postnatal exposure to the fathers9 voices was less than to the mothers9 voices, the exposures to the fathers9 voices reported in this study were sufficient to elicit ERP patterns associated with recognition memory. Differences in responses between male and female voices over the right hemisphere may indicate the development of specialization within the auditory cortex. Further investigation to quantify the amount of experience required for auditory encoding will be useful in developing assessments for infants at risk of perinatal brain injury.

125 IN VITRO AND IN VIVO EVALUATION OF A NEONATAL HIGH-FLOW NASAL CANNULA SYSTEM.

Background Humidified high flow nasal cannulae (HHNC) are used in NICUs to deliver oxygen and continuous positive airway pressure. Few data exist regarding these systems. Objective Analyze pressures delivered by the Fisher & Paykel RT329 HHNC system at varying gas flows both in vitro with varying cannula sizes and air leaks and in vivo in a neonatal piglet model. Methods In vitro: Pressure and flow derived at different points in the RT329 system were measured with a flow analyzer (Fluke Biomedical, Everett, WA) at 0%, 30%, and 50% leaks. Fixed variables included initial flow (0.5-6 lpm) and cannula size. Continuous variables included pressure and flow at various points in the system. In vivo: We measured esophageal pressures (Pes) generated at flow levels ranging from 1 to 6 lpm in seven newborn piglets. Results In vitro: Pressure delivery within the system was limited by the pop-off valve (40 cmH2O); flow delivery was preserved to the point of nasal cannula insertion. Pressure and flow delivery at the cannula end was limited at > 2 lpm. With all cannula sizes, introduction of a 30% and 50% leak resulted in > 96% and > 98% decrease in delivered pressure, respectively. With all cannulae, removal of the pop-off valve resulted in a direct increase in pressure delivery as the flow was increased: 2 lpm > 80 cmH2O, 3 lpm > 140 cmH2O, 4 lpm > 210 cmH2O, 5 lpm > 220 cmH2O, and 6 lpm > 280 cmH2O. In vivo: As HHNC flow was increased from 1 lpm to 6 lpm, mean Pes increased, but extreme variation suggests a variable leak (figure values are mean ± SD). Conclusion In vitro using the RT329 system with no leak, we saw high pressures, only limited by the pop-off valve, at flows > 2 lpm. Addition of a 30 to 50% leak at the cannula end dramatically reduced delivered pressures to

106 IMPROVED VENTILATION IN PIGLETS TREATED WITH NASAL INTERMITTENT POSITIVE PRESSURE VENTILATION VERSUS SYNCHRONIZED INTERMITTENT MANDATORY VENTILATION.

Background Nasal intermittent positive pressure ventilation (NIPPV) is used to augment continuous positive airway pressure but there is little information regarding its efficacy. Hypothesis Surfactant deficient piglets treated with NIPPV would have improved physiologic tolerance of non-invasive assisted ventilation and decreased inflammatory markers than those treated with synchronized intermittent mandatory ventilation (SIMV). Methods Two modes of assisted ventilation, NIPPV and SIMV, were compared in spontaneously breathing piglets with saline lavage induced lung injury (PaO2 < 100 torr in FiO2 1.0 for minimum of 15 minutes). Both modes were provided using the Dräger Babylog 8000. Animals were randomized to NIPPV (n = 12) or SIMV (n = 11) and were treated for 6 hours. SIMV settings were VT 8 mL/kg, PEEP 5, and rate 20. NIPPV settings were PIP 30, PEEP 5, and rate 20. Oxygen was adjusted to maintain PaO2 of 80-100 torr; PIP and rate were adjusted to alter PaCO2. Physiologic parameters and arterial blood gases were continuously monitored. Data were recorded prior to lung injury, once lung injury was achieved, and then hourly. After 6 hours of treatment, piglets were euthanized. Lung tissue was then obtained to analyze for evidence of lung inflammation, including myeloperoxidase, interleukin-8, and hydrogen peroxide levels. Inflammatory marker data were analyzed using the Kruskal-Wallis test. Physiologic data were analyzed using ANOVA. Results Inflammatory marker levels were not significantly different between the two groups. Piglets treated with NIPPV demonstrated improved arterial blood gas pH (p < .001), improved pCO2 (p = .05), and a lower set respiratory rate (p < .0001) as compared to the SIMV-treated piglets. Total respiratory rate was not different. However, the SIMV group had a lower PIP (p < .001) and improved a-A gradient (p < .001) when compared to the NIPPV group. Heart rate, mean blood pressure, and mean airway pressure were not significantly different between the groups. Conclusion Surfactant deficient piglets treated with NIPPV demonstrated more efficient gas exchange with proportionally fewer mechanical breaths. In surfactant deficient piglets, NIPPV offers an adequate and non-invasive ventilatory strategy.