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Low tidal volume ventilation induces proinflammatory and profibrogenic response in lungs of rats.

OBJECTIVE: We examined whether mechanical ventilation with low tidal volume induces polymorphonuclear infiltration and proinflammatory and profibrogenic responses in rat lungs compared dependent and nondependent lung region to expression of interleukin-1beta (IL-1beta) and alpha-1 procollagen III (PC III) mRNA. DESIGN: An experimental, randomized and controlled protocol with previously normal rats. INTERVENTIONS: Three groups of ten animals were studied. Two groups were ventilated (FIO2=0.3) in supine position for 1 h without positive end expiratory pressure, one group with a low tidal volume (6 ml/kg), and the other with a high tidal volume (24 ml/kg). In the third group animals were kept in spontaneous ventilation for 1 h. MEASUREMENTS AND RESULTS: After ventilation the right lung was used to quantify polymorphonuclear infiltration. The left lung was divided into dependent and nondependent regions, and expression of IL-1beta and PC III mRNA was quantified by northern blot analysis. The group ventilated with low tidal volume had greater polymorphonuclear infiltration IL-1beta and PC III mRNA expression than the nonventilated group. Similar results were observed with high tidal volumes. There was no difference between low and high tidal volume ventilation. Expression levels of IL-1beta and PC III mRNA were higher in the nondependent region of ventilated groups and equal in the nonventilated group. CONCLUSIONS: Even a low tidal volume mode of mechanical ventilation induces proinflammatory and profibrogenic response, with a nondependent predominance for IL-1beta and PC III mRNA expression in supine, ventilated, previously normal rats.

Animals↗

Diaphragmatic movement using ultrasound during spontaneous and mechanical ventilation: effect of tidal volume.

Using ultrasound (US) the effect of various tidal volumes on the movement of ventral, dome and dorsal parts of the right hemidiaphragm was studied, both during spontaneous and mechanical ventilation. Six healthy non-medicated volunteers who were in the supine position breathed spontaneously shallowly (tidal volume (VT) being 400 ml) (SB), and deeply (VT 1000 ml) (SB-deep). In addition, they were mechanically ventilated with intermittent positive pressure ventilation at three different VT's: 500 ml (IPPV-500), 1000 ml (IPPV-1000) and 1700 ml (IPPV-1700). The maximal movement was recorded in the ventral part in 2 volunteers during SB, in 3 during SB-deep, and in 3 and 5 subjects during IPPV-500 and IPPV-1700, respectively. The movement in dome was 100% during SB (all others standardized to this), 303 +/- 107% during SB-deep, 82 +/- 30% during IPPV-500, 165 +/- 70% during IPPV-1000 and 266 +/- 153% during IPPV-1700. An increased tidal volume is associated with an increase in the diaphragmatic movement studied by US. However, a larger VT is needed during mechanical ventilation to achieve the same amount of change as occurred with deep spontaneous breathing.

Diaphragm↗

Airway pressures, tidal volumes, and mortality in patients with acute respiratory distress syndrome.

OBJECTIVE: To determine the usual practice for setting tidal volume and other ventilatory parameters in patients with acute respiratory distress syndrome (ARDS) in the late 1990s and to determine the independent effects of these practices on intensive care unit mortality. DESIGN: Subanalysis of a prospective observational study. Multivariable logistic regression was used to analyze the effects of ventilatory management on mortality. SETTING: A total of 361 intensive care units in 20 countries in March 1998. PATIENTS: A total of 467 mechanically ventilated patients with ARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The mean tidal volume used in the first week of ARDS was 8.8 mL/kg measured body weight, and there was great variability in these tidal volumes (sd = 2.0). Tidal volumes were significantly lower in patients with (n = 265) than without (n = 202) a recorded plateau pressure (8.6 vs. 9.1 mL/kg, p = .01). The overall intensive care unit mortality rate was 60.2%. In addition to the strong influence of organ failures and higher levels of inspired oxygen, late-onset ARDS (onset after >48 hrs of mechanical ventilation; odds ratio, 2.09) was independently associated with mortality. In addition, lower levels of positive end-expiratory pressure were independently associated with higher mortality (odds ratio, 0.91; 1 cm of H2O increments). Neither inspiratory pressures nor tidal volumes were independently associated with mortality, and there was no evidence of increased mortality with the use of lower inspiratory pressures. CONCLUSIONS: This descriptive study demonstrated considerable interpatient variability in tidal volumes during the study period. In addition to traditional prognostic indicators, timing of ARDS onset and the use of low levels of positive end-expiratory pressure or no positive end-expiratory pressure during the first week may adversely influence outcome in ARDS patients.

Adult↗

Low tidal volume ventilation does not increase sedation use in patients with acute lung injury.

OBJECTIVE: Low tidal volume ventilation is associated with reduced mortality in patients with acute lung injury, yet concerns exist about patient comfort and the levels of sedation and analgesia required during its use. We compared the doses and duration of sedatives and opioid analgesics in patients receiving low vs. traditional tidal volumes at our institution. DESIGN: Secondary analysis of a randomized clinical trial. SETTING: University-affiliated county hospital in Seattle, WA. PATIENTS: Sixty-one patients with acute lung injury enrolled in the National Heart, Lung and Blood Institute's ARDS Network tidal volume trial. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-three patients were randomized to the lower tidal volume arm (6 mL/kg of predicted body weight) and 28 patients were randomized to the higher tidal volume arm (12 mL/kg of predicted body weight). There were no significant differences in the percentage of study days patients received sedatives, opioids, or neuromuscular blockade. When specific study days were examined, there were no significant differences in the proportion of patients receiving benzodiazepines, propofol, haloperidol, and opioids on days 1, 2, 3, and 7 of mechanical ventilation, nor were there differences in the doses of benzodiazepines and opioids on those days. CONCLUSIONS: At our institution, low tidal volume ventilation was not associated with increased dose or duration of sedatives in patients with acute lung injury. Sedation administration should not be considered a barrier to implementing a lung-protective ventilation strategy.

Adult↗

Effect of tidal volume and PEEP on rate of edema formation in in situ perfused canine lobes.

The effects of raising tidal volume and positive end-expiratory pressure (PEEP) on rate of edema formation were studied in in situ canine left upper lobe preparations. Edema was induced by increasing blood flow to the left upper lobe (4-8 times normal). In the same animal, at equivalent flows and microvascular hydrostatic pressures, rate of edema formation observed with larger tidal volumes was significantly higher than that observed with smaller tidal volumes (0.73 +/- 0.29 vs. 0.58 +/- 0.30, P less than 0.001). Edema was also induced under static conditions (i.e., flow = 0) over a wide range of vascular pressures. Rate of edema formation was plotted against pressure and the best-fit linear regression was obtained. The slopes (g.min-1.mmHg-1.100 g-1) of the regression lines were significantly higher with larger tidal volumes compared with smaller tidal volumes [0.106 +/- 0.010 (SE) vs. 0.081 +/- 0.009, P less than 0.01]. The pressure intercepts were not different (16.1 +/- 1.6 vs. 15.7 +/- 1.8). When mean airway pressures were increased to levels equivalent to those obtained with larger tidal volumes, but by raising end-expiratory pressures, rate of edema formation dropped to levels below base line. We conclude that increasing the amplitude of cyclic changes in lung volume increases edema formation through mechanisms that are independent of changes in operating (i.e., mean) lung volume.

Animals↗

Effects of tidal volume on work of breathing during lung-protective ventilation in patients with acute lung injury and acute respiratory distress syndrome.

OBJECTIVE: To assess the effects of step-changes in tidal volume on work of breathing during lung-protective ventilation in patients with acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS). DESIGN: Prospective, nonconsecutive patients with ALI/ARDS. SETTING: Adult surgical, trauma, and medical intensive care units at a major inner-city, university-affiliated hospital. PATIENTS: Ten patients with ALI/ARDS managed clinically with lung-protective ventilation. INTERVENTIONS: Five patients were ventilated at a progressively smaller tidal volume in 1 mL/kg steps between 8 and 5 mL/kg; five other patients were ventilated at a progressively larger tidal volume from 5 to 8 mL/kg. The volume mode was used with a flow rate of 75 L/min. Minute ventilation was maintained constant at each tidal volume setting. Afterward, patients were placed on continuous positive airway pressure for 1-2 mins to measure their spontaneous tidal volume. MEASUREMENTS AND MAIN RESULTS: Work of breathing and other variables were measured with a pulmonary mechanics monitor (Bicore CP-100). Work of breathing progressively increased (0.86 +/- 0.32, 1.05 +/- 0.40, 1.22 +/- 0.36, and 1.57 +/- 0.43 J/L) at a tidal volume of 8, 7, 6, and 5 mL/kg, respectively. In nine of ten patients there was a strong negative correlation between work of breathing and the ventilator-to-patient tidal volume difference (R = -.75 to -.998). CONCLUSIONS: : The ventilator-delivered tidal volume exerts an independent influence on work of breathing during lung-protective ventilation in patients with ALI/ARDS. Patient work of breathing is inversely related to the difference between the ventilator-delivered tidal volume and patient-generated tidal volume during a brief trial of unassisted breathing.

Acute Disease↗

Effects of tidal volume and positive end-expiratory pressure during resuscitation of very premature lambs.

BACKGROUND: Guidelines recommend neonatal resuscitation without controlling tidal volume or positive end-expiratory pressure (PEEP). However, these may improve gas exchange, lung volume and outcome. AIM: To investigate resuscitation of very premature lambs with a Laerdal bag without PEEP versus volume guarantee ventilation with PEEP. METHODS: Anaesthetized lambs (n=20) delivered at 125 d gestation were randomized to three groups receiving 15 min resuscitation: (1) Laerdal bag and no PEEP; (2) ventilation with a tidal volume of 5 ml/kg and 8 cm H(2)O PEEP; (3) ventilation with 10 ml/kg and 8 cm H(2)O PEEP. They were then all ventilated for 2 h with tidal volumes of 5 or 10 ml/kg, and 8 cm H(2)O PEEP. Ventilation parameters and blood gases were recorded. RESULTS: Different tidal volumes affected PaCO(2) within minutes, with 10 ml/kg causing severe hypocarbia. PEEP had little effect on PaCO(2). Oxygenation improved significantly with PEEP of 8 cm H(2)O, irrespective of tidal volume. CONCLUSION: Very premature lambs can be resuscitated effectively using volume-guarantee ventilation and PEEP. Tidal volumes affected PaCO(2) within minutes but had little effect on oxygenation. PEEP halved the oxygen requirement compared with no PEEP. Resuscitating premature babies with controlled tidal volumes and PEEP might improve their outcome.

Animals↗

Tidal volume and airway pressure on high frequency jet ventilation.

The principle of jet injector indicates that large tidal volumes may be delivered on high frequency jet ventilation (HFJV) without increasing airway pressure. Fifteen dogs were ventilated on HFJV in 2 separate experiments. In the first one, tidal volume was maintained constant at 10 ml/kg, while PEEP, respiratory rate, and cannula size were changed in 16 different experimental conditions. In the second experiment, driving pressure was progressively increased from 5 to 45 psig, and PEEP, respiratory rate, and injector size were changed in 32 experimental conditions. Mean airway pressure, tidal volume, driving pressure, thoracic aortic mean pressure, and abdominal aortic mean pressure were the variables measured. Tidal volume linearly increased with driving pressure, while airway pressure only increased when tidal volume exceeded 25 ml/kg. Blood pressure was inversely related to mean airway pressure. Tidal volume was twice as high with the 1.62 mm injector, as compared to the 1.06 mm injector, although resistances are 6 times higher with the smaller injector. The difference is related to the higher entrainment, which is observed when jet flow velocity increases, as is the case when the injector cannula is smaller. The experiments confirmed that HFJV follows the physical principles of jet mixing and entrainment.

Animals↗

Inspiratory time and tidal volume during intermittent positive pressure ventilation.

We measured the tidal volume achieved during intermittent positive pressure ventilation using various inspiratory times with a minimum of 0.2 seconds. Results indicate that tidal volume shows no reduction with inspiratory times down to 0.4 seconds. An inspiratory time of 0.3 seconds, however, is likely to reduce tidal volume by 8%, and at 0.2 seconds a 22% fall may be anticipated.

Humans↗

Application of the acute respiratory distress syndrome network low-tidal volume strategy to pediatric acute lung injury.

In summary, most of the available data suggest that pediatric patients should be ventilated with low tidal volumes. The 6-mL/kg IBW tidal volume strategy as used in the ARDSNet studies is a reasonable target, having since been rigorously tested in several large, clinical trials (adult and pediatric). The mortality associated with ALI in these studies has never been lower, certainly supporting continued use of the 6 mL/kg target tidal volume as the "gold standard" and, thus, eliminating any equipoise in designing a pediatric trial comparing 6 mL/kg to a larger tidal volume. With mortality rates in children from ALI nearing 8% to 22% and with no clear surrogate outcomes identified to date, the sample sizes needed to show a significant clinical effect would be prohibitively large. Nonetheless, future research should compare 6 mL/kg IBW to even smaller tidal volumes or to high frequency ventilation in an attempt to further reduce the mortality associated with ALI and ARDS in the pediatric population.

Child↗

Heliox does not affect gas exchange during high-frequency oscillatory ventilation if tidal volume is held constant.

OBJECTIVE: To compare gas exchange with heliox and oxygen-enriched air during high-frequency oscillatory ventilation, while controlling for tidal volume, in a pediatric swine model of acute lung injury. We hypothesized that when tidal volume delivery is held constant, heliox does not alter gas exchange. DESIGN: Randomized, crossover trial. SETTING: University animal research laboratory. SUBJECTS: Ten swine (4.4-5.4 kg). INTERVENTIONS: Acute lung injury (A-a gradient of >300 mm Hg) was created using repeated saline lavage during conventional mechanical ventilation. The animals were then administered high-frequency oscillatory ventilation and ventilated with 60% oxygen/40% helium and 60% oxygen/40% nitrogen in a randomized, crossover trial. When changing gas mixtures within each animal, mean airway pressure (Paw = 16.8 +/- 0.3 cm H(2)O) and frequency (10 Hz) were held constant. Oscillation amplitude (DeltaP) was adjusted to maintain constant tidal volume delivery as measured by respiratory inductive plethysmography. Next, the animals were ventilated with 40% oxygen/60% helium and 40% oxygen/60% nitrogen in a randomized crossover trial, again controlling for tidal volume. MEASUREMENTS AND MAIN RESULTS: Gas exchange was assessed by arterial blood gas analysis after ventilation with each gas mixture. We demonstrated no significant difference in Paco(2) or Pao(2) between the heliox and oxygen-enriched air with either the 40% or 60% oxygen mixtures. The oscillation amplitude required to achieve the same tidal volume delivery was significantly less with heliox. CONCLUSIONS: We conclude that if tidal volume delivery is maintained constant, heliox does not alter gas exchange when compared with oxygen-enriched air. However, to achieve the same tidal volume delivery, a lower oscillation amplitude is required with heliox. The clinical benefit of heliox administration during high-frequency oscillatory ventilation has yet to be determined. Possible advantages of heliox include improved ventilation of larger patients when approaching the power limitations of the Sensormedics 3100A oscillator and a potential reduction in the oscillation amplitude delivered to the more proximal gas exchange units.

Animals↗

[Features of the respiration of the rat at a given tidal volume].

Intact rats were trained to breathe in a given tidal volume equal to VT; 0.8 VT; 0.6 VT; 0.4 VT. To decrease their spontaneous tidal volume rats were automatically punished with electric current for exceeding the given volume. All rats could breathe in the ranges VT and 0.8 VT maintaining the obligatory level of lung ventilation. It was difficult for them to breathe in the ranges 0.6 VT and 0.4 VT. In these cases the lung ventilation was lower than the obligatory one and the breathing was interrupted with hyperpnoea. Rats respiratory reactions depend on the range of the restriction. Three types of respiratory responses to the tidal volume restriction were found. The ability of rats to breathe in given ranges of the restriction are discussed.

Animals↗

A modified Pitot tube for the accurate measurement of tidal volume in children.

A device using modification of a Pitot tube has been designed for measurement of tidal volume in infants and small children. Its accuracy was compared both n vitro and n vivo to that of a calibrated pneumotachograph (Fleish #1) designed for a similar flow range. In vitro measurement of air flow with the modified Pitot tube (MPT) was within 5% of the pneumotachograph readings over a range of 1-60 l/min. Similar accuracy was found with measurement of tidal volumes from 20 ml to 1 l, delivered by a calibrated volume-cycled ventilator using a variety of inspiratory flow rates. Tidal volume measurements with the MPT were compared to the pneumotachograph using helium, oxygen, carbon dioxide, and a range of nitrous oxide/oxygen mixtures. A manual control was incorporated into the MPT electronics to allow direct measurements of tidal volume with different nitrous oxide/oxygen concentrations. In vivo, the insertion of the MPT into the patient circuit caused no apparent changes in ventilatory parameters in children under 20 kg. Measurement of tidal volumes with the MPT agreed to within 8% of pneumotachograph readings. The low dead space (1.5 cc) and light weight (12 gm) of the MPT confer advantages over the pneumotachograph (15 ml dead space and a weight of 90 gm) for routine use in pediatric anesthesia.

Anesthesiology↗

Approximate entropy of respiratory rate and tidal volume during weaning from mechanical ventilation.

OBJECTIVE: To determine the effects of respiratory failure on respiratory rate pattern and tidal volume pattern. DESIGN: Prospective, clinical study. SETTING: Cardiovascular intensive care unit. PATIENTS: Ten patients within 12 hrs of cardiac surgery, and 21 patients who required prolonged (>7 days) mechanical ventilation. INTERVENTIONS: Patients were placed on spontaneous ventilation for weaning trials. MEASUREMENTS AND MAIN RESULTS: During spontaneous ventilation, each breath's instantaneous respiratory rate and tidal volume were recorded for later analysis. Approximate entropy (ApEn) was calculated for respiratory rate and tidal volume series of the terminal 1000 breaths on each spontaneous ventilation trial in series of 100, 300, and 1000 breaths. Ten patients (controls) were studied and extubated within 12 hrs of cardiac surgery. The other 21 patients were studied during attempts to wean them from mechanical ventilation. These patients passed (Group V-Pass) 59 and failed (Group V-Fail) 14 weaning trials. Mean tidal volume did not vary between groups, but respiratory rate increased progressively from the control group to Group V-Pass to Group V-Fail (p < .017). Conversely, approximate entropy of respiratory rate (ApEn-RR) did not vary among the three groups at any time series length, but approximate entropy of tidal volume (ApEn-VT) increased from the control group to Group V-P (p< .017) to Group V-F (p< .017) at all time series lengths. ApEn-VT was very specific but only moderately sensitive at identifying respiratory failure. CONCLUSION: Respiratory failure causes tidal volume patterns to become increasingly irregular, but increasing respiratory rate has no effect on respiratory rate pattern.

Aged↗

Postural effects on measurements of tidal volume from body surface displacements.

Tidal volume measurements based on the sum of volume displacements of the rib cage (RC) and abdomen (Ab) are limited in accuracy when changes in posture occur. To elucidate the underlying sources of error, five subjects performed spinal flexion-extension isovolume maneuvers and then performed Konno-Mead isovolume maneuvers at different lung volumes while erect, with the spine fully flexed, and at intermediate degrees of spinal flexion. RC and Ab dimensions were measured with respiratory inductance plethysmograph belts, and spinal flexion was assessed by a pair of magnetometers measuring the xiphi-Ab distance (Xi). RC and Ab volume-motion coefficients (alpha and beta, respectively) were calculated from the slope (-beta/alpha) of the Konno-Mead isovolume lines. We found that 1) spinal flexion with constant lung volume mainly increases the RC dimension, thereby displacing the Konno-Mead isovolume lines, and 2) spinal flexion decreases the -beta/alpha by decreasing beta. The error related to displacement averaged 28.4 +/- 15% of vital capacity, whereas the error related to changes in beta averaged 14 +/- 6% (SD). The systematic relationship of these errors with the degree of spinal flexion provides a mechanism whereby the addition of Xi to RC and Ab displacements significantly (P less than 0.001) improves volume estimates.

Abdomen↗

Effects of serum of the rats ventilated with high tidal volume on endothelial cell permeability and therapeutic effects of ulinastatin.

BACKGROUND: With the widespread use of ventilators in treating critically ill patients, the morbidity of ventilator-induced lung injury (VILI) is increasing accordingly. VILI is characterized by a considerable increase in microvascular leakiness and activation of inflammatory processes. In this study we investigated the effects of inflammatory mediators in VILI rat serum on endothelial cytoskeleton and monolayer cellular permeability, as well as the therapeutic effect of ulinastatin, to explore the pathogenesis and the relationship between biotrauma and lung oedema induced by VILI. METHODS: Thirty healthy male Sprague-Dawley rats were randomly divided into three groups: group A (normal tidal volume ventilation), group B (high tidal volume ventilation) and group C (high tidal volume ventilation plus ulinastatin). The serum of each rat after ventilation was added to endothelial cell line ECV-304 medium for two hours to observe the effects of serum and/or ulinastatin on endothelial fibrous actin and permeability. RESULTS: Compared to rats ventilated with normal tidal volume, serum of rats ventilated with high tidal volume caused a striking reorganization of actin cytoskeleton with a weakening of fluorescent intensity at the peripheral filament bands and formation of the long and thick stress fibres in the centre resulting in endothelial contraction and higher permeability. Prior treatment with ulinastatin lessened the above changes significantly. The changes of permeability coefficient of endothelial permeability after group A, B or C rats serum stimulation were (6.95 +/- 1.66)%, (27.50 +/- 7.77)% and (17.71 +/- 4.66)% respectively with statistically significant differences (P < 0.05) among the three groups. CONCLUSIONS: The proinflammatory mediators in the serum of the rats given high tidal volume ventilation increases endothelial permeability by reorganizing actin cytoskeleton, and pretreatment with ulinastatin lessens the permeability by inhibiting of proinflammatory mediators.

Actins↗

Expired tidal volumes measured by hot-wire anemometer during high-frequency oscillation in preterm infants.

We sought to determine the normocapnic values of expiratory tidal volume measured by hot-wire anemometer, and to evaluate how often expiratory tidal volume exceeds estimated anatomical dead space during high-frequency oscillatory ventilation (HFOV) in preterm infants. We also sought to determine the relationship between expiratory tidal volume and other respiratory parameters. The neonatal respiration monitor SLE 2100 VPM, a hot-wire anemometer, was used to measure expired tidal volume (V(T,E)) in patients ventilated by the Sensormedics 3,100A during routine clinical use of HFOV. Two hundred and fourteen simultaneous measurements of PaCO(2), V(T,E), fraction of inspired oxygen (FiO(2)), continuous distending pressure (CDP), frequency, and amplitude were obtained from 28 patients. The median birth weight was 852 g (range, 435-3,450 g), and median gestational age was 27.2 weeks (range, 23.3-41.0 weeks). One hundred and eighteen (55%) normocapnic measurements, 42 (20%) hypocapnic measurements, and 54 (25%) hypercapnic measurements were recorded in which the median V(T,E) was 1.67 ml/kg (95% confidence interval (CI), 1.55-1.79), 1.94 ml/kg (95% CI, 1.74-2.14), and 1.54 ml/kg (95% CI, 1.42-1.66), respectively. The measured V(T,E) exceeded 2.0 ml/kg in 30 instances of normocapnic V(T,E) (14%) and 54 of all V(T,E) (25%), and 3 ml/kg only in 7 (3%) and 11 (5%) instances of normocapnic and all V(T,E). There was a significant difference in median normocapnic V(T,E) obtained when FiO(2) was between 0.21-0.35, compared to values obtained when FiO(2) was 0.36-1.0 (1.61 ml/kg (95% CI, 1.52-1.70) vs. 2.06 ml/kg (95% CI, 1.93-2.19), P < 0.002). The calculated values of PaCO(2) between 35-47, using the calculated regression equation for prediction of PaCO(2) (mmHg), correctly predicted normocapnic values in 60% of measurements. Values >47 should predict hypercapnia in 81% of cases. In conclusion, expired tidal volume measurement by heated double-wire anemometer sensor is feasible, provides useful real-time information about tidal volume changes, and may improve the clinical management of HFOV.

Breath Tests↗