OBJECTIVE: It was our hypothesis that septic illness would alter both protein and energy metabolism in neonates, with elevations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) serving as markers for these effects. STUDY DESIGN: A total of 31 infants with suspected sepsis were enrolled into four groups: septic, sick-nonseptic, healthy-nonseptic, and recovered septic infants. Degree of illness, oxygen consumption, nitrogen balance, urine 3-methylhistidine/creatinine (MeH/Cr), and TNF-α, IL-6, IL-1β, and C-reactive protein (CRP) were measured. RESULTS: Oxygen consumption increased, while nitrogen balance decreased and MeH/Cr increased with increasing degree of illness. Nitrogen balance improved on recovery from sepsis. IL-6 and CRP levels were elevated in septic infants compared with sick-nonseptic and healthy infants. CONCLUSION: Neonates experience a hypermetabolic response with increased nitrogen loss during septic illness, proportional to the degree of illness. Increased delivery of protein substrate may be nutritionally advantageous to the septic neonate.

We set out to evaluate the impact of volume-targeted synchronized ventilation and conventional intermittent mandatory ventilation (IMV) on the early physiologic response to surfactant replacement therapy in neonates with respiratory distress syndrome (RDS). We hypothesized that volume-targeted, patient-triggered synchronized ventilation would stabilize minute ventilation at a lower respiratory rate than that seen during volume-targeted IMV, and that synchronization would improve oxygenation and decrease variation in measured tidal volume (V(t)). This was a prospective, randomized study of 30 hospitalized neonates with RDS. Infants were randomly assigned to volume-targeted ventilation using IMV (n = 10), synchronized IMV (SIMV; n = 10), or assist/control ventilation (A/C; n = 10) after meeting eligibility requirements and before initial surfactant treatment. Following measurements of arterial blood gases and cardiovascular and respiratory parameters, infants received surfactant. Infants were studied for 6 hr following surfactant treatment. Infants assigned to each mode of ventilation had similar birth weight, gestational age, and Apgar scores at birth, and similar oxygenation indices at randomization. Three patients were eliminated from final data analysis because of exclusionary conditions unknown at randomization. Oxygenation improved significantly following surfactant therapy in all groups by 1 hr after surfactant treatment (P < 0.05). No further improvements occurred with time. Total respiratory rate was lowest (P < 0.05) and variation in tidal volume (V(t)) was least in the A/C group (P < 0. 05). Minute ventilation (V(')(E)), delivered airway pressures, respiratory system mechanics, and hemodynamic parameters were similar in all groups. We conclude that volume-targeted A/C ventilation resulted in more consistent tidal volumes at lower total respiratory rates than IMV or SIMV. Oxygenation and lung mechanics were not altered by synchronization, possibly due to the volume-targeting strategy. Of the modes studied, A/C, a fully-synchronized mode, may be the most efficient method of mechanical ventilator support in neonates receiving surfactant for treatment of RDS.

OBJECTIVE:To test the hypothesis that perfluorocarbon (PFC) priming before surfactant administration improves gas exchange and lung compliance, and also decreases lung injury, more than surfactant alone. DESIGN:Prospective, randomized animal study. SETTING:Animal research laboratory of Children's Hospital of St. Paul. SUBJECTS:Thirty-two newborn piglets, weighing 1.55 +/- 0.18 kg. INTERVENTIONS:We studied four groups of eight animals randomized after anesthesia, paralysis, tracheostomy, and establishment of lung injury using saline washout to receive one of the following treatments: a) surfactant alone (n = 8); b) priming with the PFC perflubron alone (n = 8); c) priming with perflubron followed by surfactant (n = 8); and d) no treatment (control; n = 8). Perflubron priming was achieved by instilling perflubron via the endotracheal tube in an amount estimated to represent the functional residual capacity, ventilating the animal for 30 mins, and then removing perflubron by suctioning. After all treatments were given, animals were mechanically ventilated for 4 hrs. MEASUREMENTS AND MAIN RESULTS:We evaluated oxygenation, airway pressures, respiratory system compliance, and hemodynamics at baseline, after induction of lung injury, and at 30-min intervals for 4 hrs. Histopathologic evaluation was carried out using a semiquantitative scoring system and by computer-assisted morphometric analysis. After all treatments, animals had decreased oxygenation indices (p < .001) and increased respiratory system compliance (p < .05). Animals in PFC groups had similar physiologic responses to treatments as animals treated with surfactant only; both the PFC-treated groups and the surfactant-treated animals required lower mean airway pressures throughout the experiment (p < .001) and had higher pH levels at 90 and 120 mins (p < .05) compared with the control group. Pathologic analysis demonstrated decreased lung injury in surfactant-treated animals compared with animals treated with PFC or the controls (p < .02). CONCLUSIONS:Priming the lung with PFC neither improved the physiologic effects of exogenous surfactant nor improved lung pathology in this animal model.

This study evaluates different ventilator strategies during gas (GV) and partial liquid ventilation (PLV) in spontaneously breathing animals. We hypothesized that during PLV, spontaneously breathing animals would self‐regulate respiratory parameters by increasing respiratory rate (RR) and minute ventilation (V′E) when compared to animals mechanically ventilated with gas, and further that full synchronization of each animal's effort to the ventilator cycle would decrease RR at stable tidal volumes (VT). We studied 12 newborn piglets (1.54 ± 0.24 kg) undergoing GV and PLV in 3 different modes: intermittent mandatory ventilation (IMV), synchronized IMV (SIMV), and assist control ventilation (AC). Modes occurred sequentially in random order during GV first, with the same order then repeated during PLV. Animals initially received continuous positive airway pressure (CPAP) and returned to CPAP during PLV at the end of the experiment. Pressure‐limited, volume‐targeted ventilation was used with a tidal volume goal of 13 cc/kg. Rate was set at 10/min during IMV and SIMV, with a back‐up rate of 10/min during AC. RR, V′E, mechanical (VT) and spontaneous tidal volumes (sVT) were measured breath‐to‐breath using a computer‐assisted lung mechanics analyzer; mean values were determined over 30‐min periods. Data analysis used paired t‐tests with Bonferroni correction as needed (P < 0.05).

Surfactant followed by partial liquid ventilation (PLV) with perfluorocarbon (PFC; LiquiVent) improves oxygenation, lung compliance, and lung pathology in lung-injured animals receiving conventional ventilation (CV). In this study, we hypothesize that high-frequency oscillation (HFO) and CV will provide equivalent oxygenation in lung-injured animals following surfactant repletion and PLV, once lung volume is optimized. After saline-lavage lung injury during CV, newborn piglets were randomized to either HFO (n = 10) or CV (n = 9). HFO animals were stabilized over 15 min without optimization of lung volume; CV animals continued treatment with time-cycled, pressure-limited, volume-targeted ventilation. All animals then received 100 mg/kg of surfactant (Survanta). Thirty minutes later, all received intratracheal PFC to approximate functional residual capacity. Thirty minutes after PLV began, mean airway pressure (MAP) in both groups was increased to improve oxygenation. MAP was directly adjusted during HFO; PEEP and PIP were adjusted during IMV, maintaining a pressure sufficient to deliver 15 mL/kg tidal volume. Animals were treated for 4 h. The CV group showed improved oxygenation following surfactant administration (OI: 26.79 +/- 1.98 vs. 8.59 +/- 6.29, P < 0.0004), with little further improvement following PFC administration or adjustments in MAP. Oxygenation in HFO-treated animals did not improve following surfactant, but did improve following PFC (0I: 27.78 +/- 6.84 vs. 15.86 +/- 5.53, P < 0.005) and adjustments in MAP (OI: 15.86 +/- 5.53 vs. 8.96 +/- 2.18, P < 0.03). After MAP adjustments, there were no significant intergroup differences in oxygenation. Animals in the CV group required lower MAP than animals in the HFO group to maintain similar oxygenation. We conclude that surfactant repletion followed by PLV improves oxygenation during both CV and HFO. The initial response to administration of surfactant and PFC was different for the conventional and high-frequency oscillation groups, likely reflecting the ventilation strategy used; animals in the CV group responded most to surfactant, whereas animals in the HFO group responded most after PFC instillation. The ultimately similar oxygenation of the two groups once lung volume had been optimized suggests that HFO may be used effectively during administration of, and treatment with, surfactant and perfluorocarbon.

Partial Liquid Ventilation Using High Frequency Oscillation: Effects of Changes in Frequency on Gas Exchange. † 1593

Protein catabolism and oxygen consumption are increased in septic adults in proportion to degree of illness. Inflammatory cytokines are thought to mediate proteolysis to maintain synthesis of acute phase proteins (e.g. C-reactive protein [CRP]) during sepsis. Septic neonates have immature immunologic responses characterized by elevated IL-6, but not tumor necrosis factor (TNF) levels. To study the impact of sepsis on cytokines and protein metabolism in neonates, we studied 25 newborns (36±3 wks EGA; 2910±840g) divided into three groups: Group 1 (septic, positive blood culture [BC]), Group 2 (sick, negative BC), Group 3 (healthy, rule out sepsis). Infants had oxygen consumption (VO2 [mL/kg/min]), 6 hour nitrogen balance (N Bal[g/kg/d]), urinary 3-methyl Histidine/Creatinine (3MH/Cr), serum TNF & IL-6 (pg/mL), CRP (mg/dL), and Score for Neonatal Acute Physiology (SNAP) measured at 12-36 hours after onset of illness. Data are mean±SD.Table

Surfactant (surf, Survanta®) followed by partial liquid ventilation(PLV) with perflubron (LiquiVent®) improves lung mechanics and oxygenation more than S only, PLV only, or PLV followed by S (Peds Res 1996:39;343A). Histologic and morphometric analysis was performed on slides from the upper anterior and lower posterior lobes of 32 newborn piglets (1.7±0.8 kg) with saline lavage-induced lung injury (PaO2<60 torr, FiO2 1.0) after randomization into 4 groups and treatment for 2 hours with: 1) surf only (S; n=8); 2) PLV only (PLV; n=8); 3) PLV followed by surf (PLV-S; n=8 and 4) surf followed by PLV (S-PLV; n=8). Ventilators were adjusted to maintain tidal volume of 15 cc/kg; FiO2 was 1.0. Histologic variables (alveolar, interstitial inflammation; alveolar, interstitial hemorrhage; edema; atelectasis; necrosis) were scored on a 0-4 point scale (no injury = 0, injury in 25% of field = 1, injury in 50% of field = 2, injury in 75% of field = 3, and injury throughout field = 4). Morphometric analysis on trichrome-stained slides analyzed total cellular to air space, expressed as percent tissue area (% tissue area =[cellular area/total area] × 100). Kruskal-Wallis, Wilcoxin, and paired t-tests with Bonferroni correction (p<0.05) were used to assess differences. Table

We compared the effects of surfactant and partial liquid ventilation (PLV), and the impact of administration order, on oxygenation, respiratory system compliance (Crs), hemodynamics, and lung pathology in an animal lung injury model. We studied four groups: surfactant alone (S; n = 8); partial liquid ventilation alone (PLV-only; n = 8); surfactant followed by partial liquid ventilation (S-PLV; n = 8); and partial liquid ventilation followed by surfactant (PLV-S; n = 8). Following treatments, all animals had improved oxygenation index (OI) and Crs. Animals in PLV groups showed continued improvement over 2 h (% change OI: PLV-S -83% versus S -47%, p < 0.05; % change Crs: S-PLV 73% versus S 13%, p < 0.05). We also saw administration-order effects: surfactant before PLV improved Crs (0.92 ml/cm H2O after surfactant versus 1.13 ml/cm H2O after PLV, p < 0.02) without changing OI, whereas surfactant after PLV did not change Crs and OI increased (5.01 after PLV versus 8.92 after surfactant p < 0.03). Hemodynamics were not different between groups. Pathologic analysis demonstrated decreased lung injury in dependent lobes of all PLV-treated animals, and in all lobes of S-PLV animals, when compared with the lobes of the S animals (p < 0.05). We conclude that surfactant therapy in combination with PLV improved oxygenation, respiratory system mechanics, and lung pathology to a greater degree than surfactant therapy alone. Administration order affected initial physiologic response and ultimate pathology: surfactant given before PLV produced the greatest improvements in pathologic outcomes.

High Frequency Oscillation After Surfactant and Perfluorocarbon in an Animal Model of RDS. † 1549

We tested the hypothesis that partial liquid ventilation (PLV) with perflubron (LiquiVent®) in spontaneously breathing (SB) animals would increase respiratory rate (RR), minute ventilation (Ve), and work of breathing when compared to animals treated with gas ventilation (GV). We studied 8 newborn piglets after sedation with ketamine, intubation, and placement of catheters and an esophageal balloon. CPAP was initially used, then animals were randomized to sequentially receive different modes of ventilation during GV (Drager Babylog): IMV-SIMV-AC, or AC-SIMV-IMV. We then instilled perflubron to FRC and repeated the sequence during PLV. Animals returned to CPAP during PLV at the end of the experiment. Each treatment lasted 30 minutes. Ventilator rate during IMV and SIMV, and backup rate during AC, was 10/minute. RR, Ve, and pressure- time product (PTP=ΔPes·Ti, by flow) were measured for all spontaneous and triggered breaths. Standardized PTP•RR is an index of work of breathing. Blood gases were measured and OI calculated every 15 minutes. Reported values are means for the treatment periods. Data analysis used paired t-tests (p<0.05).Table

PARTIAL LIQUID VENTILATION AND SURFACTANT: INTERACTION AND ADMINISTRATION ORDER EFFECTS. † 2040