Akinori Uchiyama

Spontaneous breathing during lung-protective ventilation in an experimental acute lung injury model: high transpulmonary pressure associated with strong spontaneous breathing effort may worsen lung injury.

Objective: We investigated whether potentially injurious transpulmonary pressure could be generated by strong spontaneous breathing and exacerbate lung injury even when plateau pressure is limited to <30 cm H2O. Design: Prospective, randomized, animal study. Setting: University animal research laboratory. Subjects: Thirty-two New Zealand White rabbits. Interventions: Lavage-injured rabbits were randomly allocated to four groups to receive low or moderate tidal volume ventilation, each combined with weak or strong spontaneous breathing effort. Inspiratory pressure for low tidal volume ventilation was set at 10 cm H2O and tidal volume at 6 mL/kg. For moderate tidal volume ventilation, the values were 20 cm H2O and 7–9 mL/kg. The groups were: low tidal volume ventilation + spontaneous breathingweak, low tidal volume ventilation + spontaneous breathingstrong, moderate tidal volume ventilation + spontaneous breathingweak, and moderate tidal volume ventilation + spontaneous breathingstrong. Each group had the same settings for positive end-expiratory pressure of 8 cm H2O. Measurements and Results: Respiratory variables were measured every 60 mins. Distribution of lung aeration and alveolar collapse were histologically evaluated. Low tidal volume ventilation + spontaneous breathingstrong showed the most favorable oxygenation and compliance of respiratory system, and the best lung aeration. By contrast, in moderate tidal volume ventilation + spontaneous breathingstrong, the greatest atelectasis with numerous neutrophils was observed. While we applied settings to maintain plateau pressure at <30 cm H2O in all groups, in moderate tidal volume ventilation + spontaneous breathingstrong, transpulmonary pressure rose >33 cm H2O. Both minute ventilation and respiratory rate were higher in the strong spontaneous breathing groups. Conclusions: Even when plateau pressure is limited to <30 cm H2O, combined with increased respiratory rate and tidal volume, high transpulmonary pressure generated by strong spontaneous breathing effort can worsen lung injury. When spontaneous breathing is preserved during mechanical ventilation, transpulmonary pressure and tidal volume should be strictly controlled to prevent further lung injury.

The Comparison of Spontaneous Breathing and Muscle Paralysis in Two Different Severities of Experimental Lung Injury.

Objectives:The benefits of spontaneous breathing over muscle paralysis have been proven mainly in mild lung injury; no one has yet evaluated the effects of spontaneous breathing in severe lung injury. We investigated the effects of spontaneous breathing in two different severities of lung injury compared with muscle paralysis. Design:Prospective, randomized, animal study. Setting:University animal research laboratory. Subjects:Twenty-eight New Zealand white rabbits. Interventions:Rabbits were randomly divided into the mild lung injury (surfactant depletion) group or severe lung injury (surfactant depletion followed by injurious mechanical ventilation) group and ventilated with 4-hr low tidal volume ventilation with spontaneous breathing or without spontaneous breathing (prevented by a neuromuscular blocking agent). Inspiratory pressure was adjusted to control tidal volume to 5–7 mL/kg, maintaining a plateau pressure less than 30 cm H2O. Dynamic CT was used to evaluate changes in lung aeration and the regional distribution of tidal volume. Measurements and Results:In mild lung injury, spontaneous breathing improved oxygenation and lung aeration by redistribution of tidal volume to dependent lung regions. However, in severe lung injury, spontaneous breathing caused a significant increase in atelectasis with cyclic collapse. Because of the severity of lung injury, this group had higher plateau pressure and more excessive spontaneous breathing effort, resulting in the highest transpulmonary pressure and the highest driving pressure. Although no improvements in lung aeration were observed, muscle paralysis with severe lung injury resulted in better oxygenation, more even tidal ventilation, and less histological lung injury. Conclusions:In animals with mild lung injury, spontaneous breathing was beneficial to lung recruitment; however, in animals with severe lung injury, spontaneous breathing could worsen lung injury, and muscle paralysis might be more protective for injured lungs by preventing injuriously high transpulmonary pressure and high driving pressure.

Low dose intrathecal morphine and pain relief following caesarean section.

Healthy women who underwent caesarean section under spinal anaesthesia were studied to determine the extent of postoperative analgesia and side-effects produced by low doses of intrathecal morphine. Patients were randomly allocated to receive, in double-blind fashion, 0 mg (group 1: control group), 0.05 mg (group 2), 0.1 mg (group 3), or 0.2 mg (group 4) of morphine, with 10 mg tetracaine in 10% dextrose 2.5 ml. (n = 20 x 4 groups). The effect of intrathecal morphine was examined in terms of the duration until the first supplemental analgesic was needed and the numbers of the doses within the first postoperative 48 h. Pain relief was significantly greater in groups 3 and 4 than in group 1. The incidence of nausea, vomiting and pruritus increased in a dose-dependent manner. No patient developed respiratory depression. Our results suggest that postoperative analgesia lasts more than 24 h with 0.1 mg or 0.2 mg of intrathecal morphine. Since the incidence of side-effects was higher at 0.2 mg, 0.1 mg may be the optimum dose for caesarean section.

Effects of Peak Inspiratory Flow on Development of Ventilator-induced Lung Injury in Rabbits

Background: A lung-protecting strategy is essential when ventilating acute lung injury/acute respiratory distress syndrome patients. Current emphasis is on limiting inspiratory pressure and volume. This study was designed to investigate the effect of peak inspiratory flow on lung injury. Methods: Twenty-four rabbits were anesthetized, tracheostomized, ventilated with a Siemens Servo 300, and randomly assigned to three groups as follows: 1) the pressure regulated volume control group received pressure-regulated volume control mode with inspiratory time set at 20% of total cycle time, 2) the volume control with 20% inspiratory time group received volume-control mode with inspiratory time of 20% of total cycle time, and 3) the volume control with 50% inspiratory time group received volume-control mode with inspiratory time of 50% of total cycle time. Tidal volume was 30 ml/kg, respiratory rate was 20 breaths/min, and positive end-expiratory pressure was 0 cm H2O. After 6 h mechanical ventilation, the lungs were removed for histologic examination. Results: When mechanical ventilation started, peak inspiratory flow was 28.8 ± 1.4 l/min in the pressure regulated volume control group, 7.5 ± 0.5 l/min in the volume control with 20% inspiratory time group, and 2.6 ± 0.3 l/min in the volume control with 50% inspiratory time group. Plateau pressure did not differ significantly among the groups. Gradually during 6 h, Pao2 in the pressure regulated volume control group decreased from 688 ± 39 to a significantly lower 304 ± 199 mm Hg (P < 0.05) (mean ± SD). The static compliance of the respiratory system for the pressure regulated volume control group also ended significantly lower after 6 h (P < 0.05). Wet to dry ratio for the pressure regulated volume control group was larger than for other groups (P < 0.05). Macroscopically and histologically, the lungs of the pressure regulated volume control group showed more injury than the other groups. Conclusion: When an injurious tidal volume is delivered, the deterioration in gas exchange and respiratory mechanics, and lung injury appear to be marked at a high peak inspiratory flow.

Pulmonary resistance in dogs: a comparison of xenon with nitrous oxide

Xenon (Xe) may cause an increase in airway resistance due to its high density and viscosity. The object of this study was to examine the effects of Xe on pulmonary resistance using dog models with normal and methacholine-treated airways. During anaesthesia 22 mongrel dogs’ tracheas were intubated and the lungs were mechanically ventilated with 70% N2/30% O2 as a control gas. The gases 70% nitrous oxide (N2O), 50% N2O, 70% Xe and 50% Xe were administered in a random order for 25 min. Bronchoconstriction was produced by a continuous infusion of methacholine, 0.22 mg · kg−1 · hr−1. Pulmonary resistance (Rl) was calculated by the isovolume method using flow at the airway opening, volume and transpulmonary pressure. In normal dogs,Rl breathing 70% Xe (mean ± SEM, 0.84 ± 0.12 cm H2O · L−1 · sec−1) was greater (P < 0.05) than with 70% N2O, 50% N2O or control gas (0.61 ± 0.08, 0.59 ± 0.06 and 0.62 ± 0.06 cm H2O · L−1 sec−1). Breathing 50% Xe theRL (0.77 ± 0.10 cm H2O · L−1 · sec−1) was not different from 50% N2O or control. Methacholine infusion increasedRL 3.92 ± 1.98 (mean ± SD) times. TheRL breathing 50% Xe (2.55 ± 0.44 cm H2O · L−1 · sec−1) was not greater than during 50% N2O or control (2.08 ± 0.33 and 2.13 ± 0.33 cm H2O · L−1 · sec−1) in methacholine-treated dogs. The data suggest that inhalation of high concentrations of Xe increases airway resistance, but only to a modest extent in dogs with normal or methacholine-treated airways.RésuméA cause de sa densité et de sa viscosité élevées, le Xénon (Xe) peut augmenter la résistance des voies aériennes. Le but de ce travail consiste à étudier les effets du Xe sur la résistance pulmonaire de chiens aux voies aériennes normales ou traitées à la méthacholine. Pendant l’anesthésie, la trachée de 22 chiens batards est intubée et les chiens sont ventilés mécaniquement avec le gaz contrôle (70% N2/30% O2). Du protoxyde d’azote (N2O) 70%, 50% N2O, 70% Xe et 50% Xe sont administrés aléatoirement pour 25 min. La bronchoconstriction est produite par une perfusion continue de méthacholine, 0,22 mg · kg−1 · hr−1. La résistance pulmonaire (Rl) est calculée selon la méthode de lïsovolume avec la mesure du débit à l’entrée des voies aériennes, du volume et de la pression transpulmonaire. Chez les chiens normaux, laRl sous 70% Xe (moyenne ± SEM, 0,84 ± 0,12 cm H2O · L−1 · sec−1) est plus élevée (P < 0,05) qu’avec 70% N2O, 50% N2O et qu’avec le gaz contrôle (0,61 ± 0,08, 0,59 ± 0,06 et 0,62 ± 0,06 cm H2O · L−1 · sec−1). Sous 50% Xe, laRl (0,77 ± 0,10 cm H2O · L−1 · sec−1) ne diffère pas du 50% N2O ou du contrôle. La perfusion de méthacholine augmente laRl 3,92 ± 1,98 (moyenne ± SD) fois. Sous 50% Xe, laRl (2,55 ± 0,44 cmH2O · L−1 · sec−1) n’est pas plus élevée que sous 50% N2O ou que sous le gaz contrôle (2,08 ± 0,33 et 2,13 ± 0,33 cmH2O · L−1 · sec−1) chez les chiens traités à la méthacholine. Ces données suggèrent que l’inhalation de hautes concentrations de Xe augmente la résistance des voies aériennes, mais modérément seulement, chez les chiens aux des voies aériennes normales ou traitées à la méthacholine.

A Comparison of the Effects on Respiratory Carbon Dioxide Response, Arterial Blood Pressure, and Heart Rate of Dexmedetomidine, Propofol, and Midazolam in Sevoflurane-Anesthetized Rabbits

BACKGROUND: Dexmedetomidine, propofol, and midazolam are commonly used sedative-hypnotic drugs. Using a steady-state method, we examined the CO2 ventilatory response, mean arterial blood pressure (MAP) and heart rate (HR) effects of these three drugs in sevoflurane-anesthetized rabbits. METHODS: New Zealand white rabbits weighing 2.9 ± 0.2 kg (mean ± sd) were used. After anesthetic induction and tracheostomy, the animals inhaled 2% sevoflurane to ensure a stable level of sedation throughout the experiment. After preparation, the rabbits were randomly assigned to four groups (n = 10 × 4) and received the following drugs: Group C, control; Group D, dexmedetomidine infused at 2 &mgr;g · kg−1 · h−1; Group P, propofol with the plasma concentration maintained at 15 &mgr;g/mL; Group M, midazolam initial IV 0.3 mg/kg bolus dose, followed by infusion at 1.86 mg · kg−1 · h−1. At 15 minutes after the start of infusion, for 20 min periods, in random sequences, gas including 0%, 1%, 2%, 3%, 4%, or 5% of CO2 was delivered to each animal. Fraction of inspired oxygen was maintained at 0.9. We did intergroup comparisons of minute ventilation (MV), respiratory rate, MAP, and HR during the final minute of each inspiratory carbon dioxide concentration (FiCO2) period. RESULTS: For Groups P and M, the rightward shift of plots for MV against FiCO2 indicated significant respiratory depression compared with Group C. There was also significantly more depression than in Group D. We found no significant differences between Groups P and M or between Groups C and D in the plots of MV against FiCO2. No significant differences among the four groups were apparent for respiratory rate. Paco2-MV response plots were derived from linear regression analysis of data for mean MV and mean Paco2 at each FiCO2 to compute apneic CO2 thresholds and CO2 sensitivities. The apneic CO2 thresholds of Groups P and M were larger than those of Groups C and D. The CO2 sensitivities of Group D were slightly lower than in Group C. No similar significant difference between the CO2 sensitivities of other group pairs was apparent. MAP in Group D was lower than in Groups C and M. In Group D, HR was lower than in Groups C, P, and M. CONCLUSIONS: The major finding is that, during sevoflurane anesthesia in rabbits, dexmedetomidine slightly altered the ventilatory response to CO2. It decreased MAP more than propofol and midazolam, which both significantly depressed the ventilatory response to CO2.

Volume-controlled Ventilation Does Not Prevent Injurious Inflation during Spontaneous Effort

Rationale: Spontaneous breathing during mechanical ventilation increases transpulmonary pressure and Vt, and worsens lung injury. Intuitively, controlling Vt and transpulmonary pressure might limit injury caused by added spontaneous effort. Objectives: To test the hypothesis that, during spontaneous effort in injured lungs, limitation of Vt and transpulmonary pressure by volume‐controlled ventilation results in less injurious patterns of inflation. Methods: Dynamic computed tomography was used to determine patterns of regional inflation in rabbits with injured lungs during volume‐controlled or pressure‐controlled ventilation. Transpulmonary pressure was estimated by using esophageal balloon manometry [Pl(es)] with and without spontaneous effort. Local dependent lung stress was estimated as the swing (inspiratory change) in transpulmonary pressure measured by intrapleural manometry in dependent lung and was compared with the swing in Pl(es). Electrical impedance tomography was performed to evaluate the inflation pattern in a larger animal (pig) and in a patient with acute respiratory distress syndrome. Measurements and Main Results: Spontaneous breathing in injured lungs increased Pl(es) during pressure‐controlled (but not volume‐controlled) ventilation, but the pattern of dependent lung inflation was the same in both modes. In volume‐controlled ventilation, spontaneous effort caused greater inflation and tidal recruitment of dorsal regions (greater than twofold) compared with during muscle paralysis, despite the same Vt and Pl(es). This was caused by higher local dependent lung stress (measured by intrapleural manometry). In injured lungs, esophageal manometry underestimated local dependent pleural pressure changes during spontaneous effort. Conclusions: Limitation of Vt and Pl(es) by volume‐controlled ventilation could not eliminate harm caused by spontaneous breathing unless the level of spontaneous effort was lowered and local dependent lung stress was reduced.

Propofol exerts anti-inflammatory effects in rats with lipopolysaccharide-induced acute lung injury by inhibition of CD14 and TLR4 expression

We investigated the effect of propofol (Prop) administration (10 mg kg-1 h-1, intravenously) on lipopolysaccharide (LPS)-induced acute lung injury and its effect on cluster of differentiation (CD) 14 and Toll-like receptor (TLR) 4 expression in lung tissue of anesthetized, ventilated rats. Twenty-four male Wistar rats were randomly divided into three groups of 8 rats each: control, LPS, and LPS+Prop. Lung injury was assayed via blood gas analysis and lung histology, and tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels were determined in bronchoalveolar lavage fluid using ELISA. Real-time polymerase chain reaction was used to detect CD14 and TLR4 mRNA levels, and CD14 and TLR4 protein expression was determined by Western blot. The pathological scores were 1.2 ± 0.9, 3.3 ± 1.1, and 1.9 ± 1.0 for the control, LPS, and LPS+Prop groups, respectively, with statistically significant differences between control and LPS groups (P < 0.05) and between LPS and LPS+Prop groups (P < 0.05). The administration of LPS resulted in a significant increase in TNF-α and IL-1β levels, 7- and 3.5-fold, respectively (P < 0.05), while treatment with propofol partially blunted the secretion of both cytokines (P < 0.05). CD14 and TLR4 mRNA levels were increased in the LPS group (1.48 ± 0.05 and 1.26 ± 0.03, respectively) compared to the control group (1.00 ± 0.20 and 1.00 ± 0.02, respectively; P < 0.05), while propofol treatment blunted this effect (1.16 ± 0.05 and 1.12 ± 0.05, respectively; P < 0.05). Both CD14 and TLR4 protein levels were elevated in the LPS group compared to the control group (P < 0.05), while propofol treatment partially decreased the expression of CD14 and TLR4 protein versus LPS alone (P < 0.05). Our study indicates that propofol prevents lung injury, most likely by inhibition of CD14 and TLR4 expression.

Perioperative Use of High-frequency Oscillation Immediately after Birth in Two Neonates with Congenital Cystic Adenomatoid Malformation

Congenital cystic adenomatoid malformation of the lung (CCAM) is a rare pulmonary malformation, often associated with pulmonary hypoplasia due to compression by cysts. We report two fetuses prenatally diagnosed as having CCAM who were successfully managed with high frequency oscillation

Physiologic effects of transtracheal open ventilation in postextubation patients with high upper airway resistance.

ObjectiveTo investigate whether transtracheal open ventilation (TOV), pressure control ventilation (PCV) through a minitracheotomy tube (internal diameter 4 mm), is an effective method of inspiratory assistance under high upper airway resistance in postextubation patients; to compare, in a lung model study, TOV with other methods. DesignClinical study: A prospective, controlled, crossover study. Lung model study: A prospective laboratory trial. SettingClinical study: A six-bed general intensive care unit in a teaching hospital. Lung model study: Animal research laboratory. PatientsClinical study: Eleven postextubation patients, who had undergone minitracheotomy for sputum retention between January 1997 and December 1997. SubjectLung model study: Two-bellows-in-a-box lung model, which included ordinary and high levels of upper airway resistance. InterventionsClinical study: Ventilatory settings were: assist/control (A/C) mode, 2 breaths/min of A/C back-up rate, 35–40 cm H2O of PCV, 0.6–0.8 secs of inspiratory time, and 0 cm H2O of positive end-expiratory pressure. The ventilatory parameters of TOV were compared with those of spontaneous breathing (SB). Lung model study: Effect of TOV on inspiratory assistance was compared with those of SB, open minitracheotomy, 5 L/min of transtracheal gas insufflation, and 5 and 10 cm H2O of pressure support ventilation (PSV), which simulated noninvasive positive ventilation. TOV ventilatory settings were: A/C mode; 30, 40, and 50 cm H2O of PCV, 0.9 secs of inspiratory time, and 0 cm H2O of positive end-expiratory pressure. At each ventilatory setting, we adjusted the inspiratory effort of the model to give a tidal volume of 0.5 L. Measurements and Main Results Clinical study: TOV was performed for 76.6 ± 38.6 hrs (mean ± sd) over 5.6 ± 2.6 days without major complication. Peak tracheal pressure, which was measured distal to the minitracheotomy tube in six patients by a catheter pressure transducer, was 4.33 ± 0.59 cm H2O. Inspiratory tidal volume delivered by the ventilator was 0.51 ± 0.06 L. Respiratory rate during TOV was lower than during SB. According to esophageal pressure and respiratory inductive plethysmography, TOV reduced the patient’s inspiratory work and improved the breathing pattern. Lung model study: Mean tracheal pressure during TOV and 10 cm H2O of PSV were positive values and they had larger inspiratory assistance according to the pressure-time product of pleural pressure. Although high upper airway resistance reduced the inspiratory assistance of PSV, it did not change the effects of TOV. ConclusionsTOV effectively reduced patient’s inspiratory work and was more useful than open minitracheotomy and transtracheal gas insufflation. TOV also improved the breathing pattern. TOV may be useful for resolving some postextubation respiratory problems and avoiding the need for reintubation.