Partial liquid ventilation: a comparison using conventional and high-frequency techniques in an animal model of acute respiratory failure.

OBJECTIVE: To test the hypothesis that high-frequency ventilation (HFV), when compared with conventional techniques, enhances respiratory gas exchange during partial liquid ventilation (PLV). DESIGN: A four-period crossover design. SETTING: Animal research laboratory of Children's Health Care-St. Paul. SUBJECTS: Thirty-two newborn piglets, weighing 1.40 +/- 0.39 kg. INTERVENTIONS: Animals were divided into four groups of eight animals: a) PLV with high-frequency jet ventilation; b) PLV with jet ventilation using a background intermittent mandatory ventilation (IMV) rate; c) PLV with high-frequency oscillation; or d) PLV with high-frequency flow interruption using a background IMV rate. After anesthesia, paralysis, and tracheotomy, a normal saline wash procedure produced lung injury. Perfluorocarbon was then instilled via the endotracheal tube in an amount estimated to represent functional residual capacity. Animals received randomly either PLV using conventional techniques or PLV using the selected HFV technique as initial treatment. Then, animals were crossed over to the alternative treatment at equal mean airway pressure, as measured at the endotracheal tube tip. This sequence was repeated for a total of four crossover periods, such that all animals were treated twice with PLV using conventional techniques and twice with PLV using HFV. MEASUREMENTS AND MAIN RESULTS: We measured airway pressures at the endotracheal tube tip, aortic and central venous blood pressures, arterial blood gases, and respiratory system mechanics at baseline, after induction of lung injury, and at specified intervals throughout the experiment. Measurements were made before and 15 mins after crossovers, then ventilators were adjusted to normalize gas exchange. Measurements were again made 30 mins later, at the end of the treatment period. All types of PLV provided adequate gas exchange. Only PLV using jet ventilation with IMV produced gas exchange equal to that seen during PLV using conventional techniques at equivalent mean airway pressure. By the end of the treatment periods, only PLV using high-frequency oscillation continued to require higher airway pressure than PLV using conventional techniques for equivalent gas exchange. CONCLUSIONS: Gas exchange was not enhanced during PLV-HFV. Application of HFV with PLV provides no clear acute physiologic advantages to PLV using more conventional techniques.

Lower respiratory rates without decreases in oxygen consumption during neonatal synchronized intermittent mandatory ventilation.

OBJECTIVE: We tested the hypothesis that synchronization to patient effort during intermittent mandatory ventilation (SIMV), when compared to conventional unsynchronized intermittent mandatory ventilation (IMV), will decrease energy expenditure, as reflected by decreased oxygen consumption (VO2). DESIGN: We used a four-period crossover design. Each patient was studied over four 30-min continuous time intervals. Patients were randomized to receive initially IMV or SIMV, then crossed over such that each patient was treated twice with each modality. Data were analyzed using an analysis of variance technique. SETTING: Patients were receiving treatment in the newborn intensive care unit of Children's Hospital, St. Paul. PATIENTS: We studied 17 patients, who ranged from 23 to 37 weeks gestation, were < or = 14 days old, and had study weights from 623 to 3015 g. All were mechanically ventilated for hyaline membrane disease. MEASUREMENTS AND RESULTS: We measured and compared VO2, carbon dioxide consumption (VCO2), minute ventilation (VE), total respiratory rate, heart rate, arterial blood pressure, and arterial oxygen saturation (SaO2) values during IMV and SIMV. Total respiratory rate fell significantly during SIMV (73 +/- 26 during IMV, 57 +/- 17 during SIMV, p < 0.01) in spite of no significant change in VO2 (0.6 +/- 0.16% fall in VO2 during SIMV) or VCO2 (4.2 +/- 0.19% increase in VCO2 during SIMV) values. Moreover, there were no significant differences in heart rate, blood pressure, VE, or SaO2 values with either form of therapy. CONCLUSIONS: Though total respiratory rate fell, these data do not support the hypothesis that SIMV significantly reduces respiratory rate by decreasing oxygen consumption and carbon dioxide production during infant mechanical ventilation. Rather, the marked fall in respiratory rate may be due to a more efficient respiratory pattern.

Munchausen syndrome by proxy: a profile for medical child abuse.

The term Munchausen Syndrome by Proxy describes a pattern of physical abuse in which a perpetrator produces or fabricates illness in a victim. Victims are almost always children. We alternatively call this behaviour medical child abuse. Our report describes five recent cases. Two presented with infantile apnoea, one with alleged hypoventilation, one with recurrent vomiting and one with recurrent infections. Three of the perpetrators were mothers, two were fathers. In three cases diagnoses were confirmed by covert video surveillance. Contrary to popular beliefs, this behaviour is not rare and is not a syndrome of any known psychopathology. It is simply another, very dangerous, form of child abuse. Reported victim mortalities range from 9% to 31%. To ensure child safety we suggest the medical, legal and law enforcement communities begin to view this entity more as a profile of criminal abusive behaviour and less as a medical syndrome.

Metabolic response of preterm infants to variable degrees of respiratory illness.

In older children and adults, physiologic instability associated with severe illness causes increased cellular oxygen consumption (VO2), increased serum lactate and cortisol levels, and more negative nitrogen balance. To determine the metabolic response of preterm infants to severity of respiratory illness, we analyzed VO2, nitrogen balance, urinary 3-methyl-histidine and norepinephrine concentrations, and serum levels of lactate and cortisol as a function of ventilatory index (VI). Twelve 2-day-old premature infants who were appropriate in size for gestational age (mean +/- SEM birth weight: 1460 +/- 251 gm) and who required mechanical ventilation for respiratory distress syndrome had VO2 and carbon dioxide production measured by indirect calorimetry and blood and urine samples obtained concurrently. All infants received amino acids, 1.0 gm/kg per day, and a mean energy intake of 27 +/- 3 kcal/kg per day, provided as a parenteral dextrose solution. The resting energy expenditure exceeded energy intake in all infants. The VO2 value ranged from 5.5 to 9.2 ml/kg per minute and was directly correlated with VI (r = 0.79; p = 0.002). Nitrogen balance ranged from -160 to 53 mg/kg per day (mean: -33 +/- 21 mg/kg per day) but was not dependent on VI (r = 0.04) or VO2 (r = 0.01). The serum lactate level correlated directly with VI (r = 0.82; p = 0.002) and VO2 (r = 0.60; p = 0.05), but cortisol and urinary norepinephrine levels did not. We conclude that preterm infants with respiratory distress syndrome have increased VO2 rates and serum lactate concentrations directly related to the degree of respiratory illness. They are generally in a state of mildly negative nitrogen balance, the degree of which is not related to severity of illness. Although these infants may require increased energy delivery during illness, they do not appear to require excessive amounts of amino acids.

The effects of bedside pulmonary mechanics testing during infant mechanical ventilation: a retrospective analysis.

We examined the effects of regular bedside testing of pulmonary mechanics (PM) on the outcome of 468 acutely ill, mechanically ventilated neonates. During the first of two 18-month study periods, 217 infants were mechanically ventilated without the assistance of PM measurements. During the second 18-month period, 251 infants were ventilated with the assistance of at least daily PM measurements. Using data obtained from the PM tests, we adjusted the infants' ventilators to maintain tidal volume, inspiratory time, and pressure-volume loops within predetermined limits. With the exception of the PM measurements, given the limitations of retrospective analyses, both groups of infants received identical medical and nursing care. The infants ventilated with the assistance of PM testing developed fewer pneumothoraces (4.0%; 10/251) vs. no PM testing, 10.1% (22/217); P < 0.05 by Chi-square analysis]. Infants weighing less than 1,500 g ventilated with the assistance of PM measurements had less intraventricular hemorrhage (IVH) overall, most notably, less grades I and II IVH (total IVH-PM testing, 39.1% vs. no PM testing, 65.7%; P < 0.01; Grades I-II IVH-PM testing, 30.4% vs. no PM testing, 54.9%; P < 0.01). IVH incidence was decreased independent of pneumothorax occurrence. Survival rates, incidences of bronchopulmonary dysplasia, and durations of mechanical ventilation and hospitalization were similar. This retrospective analysis suggests that PM testing during infant mechanical ventilation reduces common acute ventilator-associated complications.

Alterations in feline tracheal permeability after mechanical ventilation.

OBJECTIVES: Previous investigations of ventilator-induced airway injury focused on histopathologic changes associated with various ventilators and strategies for their use. We hypothesized that mechanical ventilation is associated with alterations in tracheal epithelial permeability, and designed a study using an animal model to evaluate changes in tracheal epithelial permeability after administering different types of mechanical ventilation to test this hypothesis. DESIGN: Prospective, multiple-group, controlled trial. Five groups of animals were studied and compared. Eight animals were studied without intubation or mechanical ventilation. A total of 28 animals (seven in each group) were studied after conventional mechanical ventilation, high-frequency positive-pressure ventilation, high-frequency jet ventilation, or high-frequency flow interruption at respiratory rates of 20, 150, 400, and 900 breaths/min, respectively. Comparison of data for each group was done using the Kruskall-Wallis analysis of variance. Between-group comparisons were made using standard error of the mean comparisons. For airway pressures and other physiologic data, one-way analysis of variance was performed. Between-group comparisons were made using the Student-Newman-Keuls' test. SETTING: Small animal physiology laboratory. SUBJECTS: Thirty-six adult cats. INTERVENTIONS: Mechanically ventilated animals were treated for 8 hrs and then killed. Inspired oxygen concentration, BP, and mean airway pressures were comparable in mechanically ventilated animals. Spontaneously breathing control animals were killed without endotracheal intubation or exposure to mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Permeability values in isolated tracheal segments were calculated for 14C-sucrose, 3H-inulin, and fluorescein isothiocyanate-dextran-20. Tracheal epithelial permeability to all studied molecules increased after exposure to mechanical ventilators. These different mechanical ventilators increased epithelial permeability in a progressive manner that paralleled ventilatory frequency. The changes were greatest after ventilation at the highest frequency. These observed changes in tracheal permeability are consistent with previously observed alterations in tracheal histopathology after exposure to mechanical ventilation. CONCLUSIONS: Mechanical ventilation was associated with increases in tracheal permeability to large and small nonionic molecules. These changes occurred with all studied ventilators, used as they are clinically. Permeability changes paralleled ventilatory rate changes.

Effect of rapid thoracic compression on the cerebral blood flow-velocity patterns of small infants.

We measured the middle cerebral artery (MCA) flow-velocities of 12 small infants (mean weight, 2,882 +/- 602 g) before, during, and after the rapid thoracic compression (RTC) maneuvers of partial forced expiratory flow-volume studies. Cerebral flow-velocities were measured using transcranial Doppler ultrasonography. RTC increased MCA end diastolic flow-velocities and Pourcelot indices of all infants (P less than 0.001). These values returned to baseline immediately after the release of chest compression. We also measured the MCA flow-velocities of several preterm infants during their normal daily activities. The changes in flow-velocity patterns observed during normal daily life were similar to those observed during RTC. These findings demonstrate that RTC produces real, but likely not pathologic, changes in cerebral blood flow-velocities.

Acute airway injury during high-frequency jet ventilation and high-frequency oscillatory ventilation.

BACKGROUND AND METHODS: We compared tracheal histologic injury patterns, airway pressure (Paw) requirements, and in vivo and in vitro estimate of airway humidification in 13 adult cats with normal lungs mechanically ventilated for 16 hr. Six animals were treated with high-frequency jet ventilation at 400 breaths/min and seven animals with high-frequency oscillatory ventilation at 900 breaths/min. RESULTS: Peak airway pressure, Paw, mean Paw, and end-expiratory pressure requirements were significantly higher for high-frequency oscillatory ventilation as compared with high-frequency jet ventilation for similar gas exchange (p less than .01). While in vivo estimates of airway humidification suggested progressively greater H2O delivery into the respirator circuit, and therefore the airway, with higher frequencies, the in vitro study suggested similar relative humidities of the delivered gases during both types of mechanical ventilation. Tracheal injury, measured using a semiquantitative scoring system, was scored similarly for both ventilators studied despite the higher pressure requirements seen with the high-frequency oscillator. CONCLUSIONS: In this animal model, high-frequency ventilation using either jet or oscillation techniques produced similar inflammatory tracheal damage despite differences in Paw exposure and humidity.

Effect of spontaneous and mechanical breathing on dynamic lung mechanics in hyaline membrane disease.

We measured then compared the dynamic lung mechanics of spontaneous breaths and mechanical breaths in 9 mechanically ventilated neonates with hyaline membrane disease. All were receiving intermittent mandatory ventilation. All breathed spontaneously between ventilator breaths. Tidal volume, transpulmonary pressure, dynamic lung compliance, airways resistance, and peak inspiratory and peak expiratory gas flows were determined for both the mechanical and the spontaneous breaths. The mechanical breaths consistently had larger tidal volumes, higher transpulmonary pressures, higher airway resistance, and lower lung compliance values (P less than 0.05). Peak inspiratory and expiratory gas flows were also higher (P less than 0.01) during mechanical breathing. The spontaneous breaths generated by patients and the mechanical breaths generated by mechanical ventilators are different. The lung mechanics measurements of these two different types of breathing should be collected, analyzed, and reported separately.

Determining optimum inspiratory time during intermittent positive pressure ventilation in surfactant-depleted cats.

This study compares two methods of selecting inspiratory time (Ti) during mechanical ventilation. One selects a standard Ti producing a brief inspiratory pressure plateau (P). The other uses simultaneous pressure, flow and tidal volume (VT) waveforms, generated by a computer-assisted lung mechanics analyzer, to reduce Ti to the point where Vt ceases to accumulate and flow returns to zero. This method does not produce a pressure plateau (NP). Following saline lung washout, ten intubated, paralyzed surfactant-depleted cats were ventilated with pressure-preset infant ventilators at constant measured VT and rates. Five animals were initially ventilated with P (Ti = 0.98 +/- 0.02 s) and five with NP (Ti = 0.77 +/- 0.10 s). Ti was then varied to produce P or NP by using a four-period crossover design. All other ventilator variables remained constant. Intravascular pressures, thermodilution cardiac outputs, arterial and mixed venous blood gases and oxygen saturations, airway pressures, Ti, VT, and gas flows were measured; respiratory system mechanics, alveolar-arterial oxygen gradients, and intrapulmonary shunts were determined for each study period. When P and NP states were compared, only mean airway pressures differed (10.1 vs. 8.9 cmH2O; P less than 0.001). Blood gas values, intravascular pressures, cardiac output, and respiratory system mechanics were all similar. Under the conditions of this study, there was no advantage to prolonging Ti beyond the point where VT ceased to accumulate.

Comparison of high-frequency oscillatory ventilation and high-frequency jet ventilation in cats with normal lungs.

Four adult cats received alternating high-frequency oscillatory ventilation (HFOV) and high-frequency jet ventilation (HFJV) at equivalent proximal airway pressures. Physiologic measurements were made before and after each ventilator change. Proximal airway pressures were then adjusted as necessary to reestablish normal pH and PaCO2 values. Aortic, pulmonary artery, and central venous pressures were monitored. Cardiac outputs were measured. Pulmonary and systemic vascular resistance, intrapulmonary shunt, and alveolar-arterial oxygen gradient were determined. Following the change from HFOV to HFJV at similar proximal airway pressures, HFJV always produced higher pH values (P less than 0.0001), higher PaO2 values (P less than 0.05), lower PaCO2 values (P less than 0.0001), as well as higher cardiac outputs (P less than 0.01), lower pulmonary artery pressures (P less than 0.001), and lower pulmonary vascular resistances (P less than 0.001). Following the reciprocal crossover, from HFJV to HFOV, HFJV pH values were again higher (P less than 0.001), and PaCO2 values were again lower (P less than 0.001). A comparison of HFOV and HFJV at similar pH and PaCO2 values showed that HFOV consistently required higher peak inspiratory pressures (P less than 0.001), higher mean airway pressure (P less than 0.001), and higher pressure wave amplitudes (P less than 0.001). Under the circumstances of this study, HFJV produced better gas exchange at lower proximal airway pressures.

Identifying lung overdistention during mechanical ventilation by using volume-pressure loops.

We measured the pulmonary mechanics of 23 mechanically ventilated neonates. Airway pressures, inspiratory and expiratory flows were simultaneously measured. Values for respiratory system mechanics were then derived from these data by using a personal computer and a special software program. Volume-pressure (V-P) loops and respiratory system compliance values were determined for representative mechanical breaths. Twelve infants had normal-appearing V-P loops. Eleven had V-P loops characteristic of lung overdistention, showing decreasing changes in volume with progressive increases in pressure. To quantify this visual observation, we determined the change in compliance during the last 20% of inspiration (C20). We then compared this value to the total compliance value for the entire breath (C) using the ratio C20/C. Mean values for C, C20, and C20/C were compared for the two patient groups. Total respiratory system compliance values were similar. C20 values were decreased in those patients with V-P loops showing overdistention. C20/C values were significantly decreased in those patients with V-P loop evidence of overdistention. Patients with V-P loop evidence of overdistention all had C20/C values less than 0.8. Those with normal-appearing V-P loops all had C20/C values greater than 1.0. The C20/C ratio appears to effectively quantitate visual V-P loop evidence of lung overdistention during mechanical ventilation.

Necrotizing tracheobronchitis: a newly recognized cause of acute obstruction in mechanically ventilated neonates.

Necrotizing tracheobronchitis (NTB) is an acute inflammatory lesion of the lower airway which can result in total airway obstruction. While potentially treatable, this lesion has been described predominantly in autopsy or animal studies. We observed clinical symptoms which reflect development of this lesion. Symptoms of acute airway obstruction (hypercarbia, respiratory acidosis, decreased chest wall movement) occurred in eight neonates undergoing treatment with high-frequency jet ventilation; five patients treated with HFJV were studied without signs of obstruction. Emergency bronchoscopy using a rigid bronchoscope was performed in the intensive care unit. The diagnosis of NTB was made by the observation of hyperemia, intraluminal debris, or the appearance of eschar formation. Necrotic debris was removed using forceps and/or suction as necessary. All patients survived treatment. Seven were long-term survivors, all with bronchopulmonary dysplasia. In patients who died, autopsy evaluation of the airway revealed a characteristic picture consisting of necrosis, neutrophil infiltration, epithelial erosion, and intraluminal obstruction.

Hypercarbic ventilatory responses of infants at risk for SIDS.

We examined the hypercarbic ventilatory responses (HVR) of 143 infants at risk for sudden infant death syndrome (SIDS) and 34 normal control infants. Sixty-five of the at-risk infants had experienced apparent life-threatening events (ALTE), and 78 were siblings of SIDS victims. Twenty-three (35%) of the ALTE infants experienced subsequent apnea; one died of SIDS. Seven (9%) of the SIDS siblings experienced subsequent apnea; two ultimately died of SIDS. In the HVR studies, we measured tidal volume (VT), minute ventilation (VE), frequency of breathing (f), and end-tidal PCO2 (PETCO2) at rest and while breathing 2% and 4% CO2. Mean HVR vales for the ALTE, sibling, and control groups were all similar. The mean HVR values for those at-risk infants who experienced subsequent apnea were not different from those who did not experience subsequent apnea. However, those infants experiencing subsequent apnea had higher mean VT/kg values (P less than 0.01) and lower mean PETCO2 values (P less than 0.001) than those who did not. The SIDS siblings had significantly lower resting VT/kg values than either the near-miss infants or normal controls (P less than 0.01). We did not find depressed HVR values in infants at risk for SIDS. On the contrary, those infants who experienced subsequent apnea had evidence suggesting relative hyperventilation. SIDS siblings had evidence suggesting relative hypoventilation. These findings are interesting and thought-provoking. However, HVR studies do not appear to be sensitive, specific, or appropriate for the general screening of infants at risk for SIDS.

Short-term dexamethasone therapy for bronchopulmonary dysplasia: acute effects and 1-year follow-up.

Eight ventilator-dependent infants with bronchopulmonary dysplasia (BPD) were treated with dexamethasone (0.5 mg/kg/day). Therapy was initiated at 19.3 +/- 3.9 days of age, continued at the initial dose for 7 days, then tapered over 2 weeks. The clinical course of these infants with BPD was compared to that of 8 similar ventilator-dependent infants with uncomplicated hyaline membrane disease (HMD). At study entry, the BPD patients had significantly higher ventilator rates, peak inspiratory pressures, mean airway pressures, alveolar-arterial oxygen gradients and fraction of inspired oxygen (FiO2) values. After 7 days of dexamethasone therapy, ventilator rates, peak inspiratory pressures, mean airway pressures, FiO2 values and alveolar-arterial oxygen gradients improved significantly. At this time, ventilator rates, peak inspiratory pressures and FiO2 values were similar to those of patients with uncomplicated HMD. BPD patients were extubated after 6.5 +/- 2.4 days of therapy. The incidences of septicemia, rickets and retinopathy of prematurity were similar in the BPD and uncomplicated HMD patients. Most dexamethasone-treated patients developed arterial hypertension during the first 48 h of therapy. Blood pressures returned to normal within 7 days of stopping therapy. All BPD patients had cosyntropin responses tested 5.5 +/- 2.6 weeks after stopping therapy. Six were normal. Two had inadequate responses. At 1 year adjusted age, the dexamethasone-treated BPD infants and HMD infants had similar radiographic bone ages, similar growth patterns and similar scores on the Bayley infant development scale. Dexamethasone was useful in the treatment of early BPD. Used as short-term therapy, the drug had minimal complications and no long-term sequelae.

Neonatal transcutaneous arterial oxygen saturation monitoring.

Transcutaneous arterial oxygen saturation (TcSaO2) and directly measured oxygen saturation values from 25 neonates with a variety of respiratory problems were compared. At arterial oxygen saturations above 60 per cent, TcSaO2 measurements were accurate and reliable. However, SaO2 values less than 60 per cent were significantly overestimated by TcSaO2, so careful laboratory confirmation of low SaO2 values is necessary. The use, accuracy, and limitations of this noninvasive transcutaneous technique for measuring arterial hemoglobin-oxygen saturation are discussed.