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Ventilation with lower tidal volumes versus traditional tidal volumes in adults for acute lung injury and acute respiratory distress syndrome.

BACKGROUND: Patients with acute respiratory distress syndrome and acute lung injury require mechanical ventilatory support. Acute respiratory distress syndrome and acute lung injury are further complicated by ventilator-induced lung injury. Lung-protective ventilation strategies may lead to improved survival. OBJECTIVES: To assess the effects of ventilation with lower tidal volume on morbidity and mortality in patients aged 16 years or older affected by acute respiratory distress syndrome and acute lung injury. A secondary objective was to determine whether the comparison between low and conventional tidal volume was different if a plateau airway pressure of greater than 30 to 35 cm H20 was used. SEARCH STRATEGY: We searched The Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library issue 4, 2003; MEDLINE (1966 to October 2003); EMBASE and CINAHL (1982 to October 2003); intensive care journals and conference proceedings; databases of ongoing research, reference lists and 'grey literature'. SELECTION CRITERIA: Randomized trials comparing ventilation using either lower tidal volume or low airway driving pressure (plateau pressure 30 cm H(2)O or less), resulting in tidal volume of 7 ml/kg or less versus ventilation that uses Vt in the range of 10 to 15 ml/kg, in adults (aged 16 years or older). DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Wherever appropriate, results were pooled. Fixed and random effects models were applied. MAIN RESULTS: Five trials, involving 1202 patients, were eligible. Mortality at day 28 was significantly reduced by lung-protective ventilation: relative risk 0.74 (confidence interval 0.61 to 0.88), whereas beneficial effect on long-term mortality was uncertain: relative risk 0.84 (confidence interval 0.68 to 1.05). The comparison between low and conventional tidal volume was not significantly different if a plateau pressure less than or equal to 31 cm H2O in control group was used: relative risk 1.13 (confidence interval 0.88 to 1.45). There was insufficient evidence about morbidity and long term outcomes. REVIEWERS' CONCLUSIONS: Clinical heterogeneity, such as different lengths of follow up and higher plateau pressure in control arms in two trials make the interpretation of the combined results difficult. Mortality is significantly reduced at day 28 and the effects on long term mortality are uncertain, although the possibility of a clinically relevant benefit cannot be excluded.

Adult↗

Ventilation with lower tidal volumes versus traditional tidal volumes in adults for acute lung injury and acute respiratory distress syndrome.

BACKGROUND: Patients with acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) require mechanical ventilatory support. ALI/ARDS is further complicated by ventilator-induced lung injury. Lung-protective ventilation strategies may lead to improved survival. OBJECTIVES: To assess the effects of ventilation with lower tidal volume (Vt) on morbidity and mortality in adults patients affected by ALI/ARDS. A secondary objective was to determine whether the comparison between low and conventional Vt is different if a plateau airway pressure of greater than 30 to 35 cm H20 was used. SEARCH STRATEGY: We searched The Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library issue 3, 2002; MEDLINE (1966 to June 2002); EMBASE and CINAHL (1982 to June 2002); intensive care journals and conference proceedings; databases of ongoing research, reference lists and 'grey literature'. SELECTION CRITERIA: Randomized trials comparing ventilation using lower Vt and/or low airway driving pressure (plateau pressure 30 cm H2O or less), resulting in Vt of 7 ml/kg or less versus ventilation that uses Vt in the range of 10 to 15 ml/kg, in adults (16 year-old or greater). DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Wherever appropriate, results were pooled. Fixed and random effects models were applied. MAIN RESULTS: Five trials, involving 1202 patients, were eligible. The test for heterogeneity gave a P-value of 0.12. Ventilation with lower Vt was associated with a decreased mortality at the end of the follow up period for each trial: 216/605 (35.7%) versus 249/597 (41.7%), relative risk (RR) 0.85 (CI 0.74 to 0.98). The effect of the intervention was not statistically significant when a random effects model was used: RR 0.91 (CI 0.72 to 1.14). Mortality at day 28 was significantly reduced by lung-protective ventilation: RR 0.74 (CI 0.61 to 0.88). The comparison between low and conventional Vt was not significantly different if a plateau pressure less than or equal to 31 cm H2O in control group was used: RR 1.13 (CI 0.88 to 1.45). There was insufficient evidence about morbidity and long term outcomes. REVIEWER'S CONCLUSIONS: Clinical heterogeneity, such as different lengths of follow up and higher plateau pressure in control arms in two trials make the interpretation of the combined results difficult. Mortality is significantly reduced at day 28 and the effects on long term mortality are uncertain, although the possibility of a clinically relevant benefit cannot be excluded. There is no evidence that low Vt ventilation is beneficial in patients where hypercapnia is potentially harmful.

Adult↗

Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.

BACKGROUND: Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome. We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients. METHODS: Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter, randomized trial. The trial compared traditional ventilation treatment, which involved an initial tidal volume of 12 ml per kilogram of predicted body weight and an airway pressure measured after a 0.5-second pause at the end of inspiration (plateau pressure) of 50 cm of water or less, with ventilation with a lower tidal volume, which involved an initial tidal volume of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less. The primary outcomes were death before a patient was discharged home and was breathing without assistance and the number of days without ventilator use from day 1 to day 28. RESULTS: The trial was stopped after the enrollment of 861 patients because mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes (31.0 percent vs. 39.8 percent, P=0.007), and the number of days without ventilator use during the first 28 days after randomization was greater in this group (mean [+/-SD], 12+/-11 vs. 10+/-11; P=0.007). The mean tidal volumes on days 1 to 3 were 6.2+/-0.8 and 11.8+/-0.8 ml per kilogram of predicted body weight (P<0.001), respectively, and the mean plateau pressures were 25+/-6 and 33+/-8 cm of water (P<0.001), respectively. CONCLUSIONS: In patients with acute lung injury and the acute respiratory distress syndrome, mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use.

Barotrauma↗

A comparison of the effects of high frequency--low tidal volume and low frequency--high tidal volume mechanical ventilation.

Ten neonates with severe lung disease were studied while mechanically ventilated with standard volume preset infant ventilators, using two different ventilatory patterns. Slow ventilatory rates and high tidal volumes were alternated with rapid rates and low tidal volumes; minute ventilation, FIo2, PEEP, and I:E ratios were held constant. Peak inspiratory pressure, mean airway pressure, expiratory time, Pao2, Paco2, pH, and arterial blood pressure were measured and compared for each frequency-tidal volume combination. The best arterial oxygenation occurred at the combination of settings that produced the highest mean airway pressure and always during low frequency-high tidal volume ventilation (P less than 0.001). Changes in oxygenation appeared to be directly related to changes in MAP. A second experiment examined two different ventilator systems' responses to changes in ventilatory rate. When the rate of one ventilator (Bourns LS104 volume preset) was increased, MAP increased. When the rate of the other ventilator (Bennett PR2 pressure preset) increased, MAP decreased. These observations suggest that there is a direct relationship between MAP and orterial oxygenation, and that the supposed advantages of one ventilatory pattern over the other may be secondary to inadvertent changes in subtle pressure-time relationships within the respiratory cycle and incidental changes in MAP. These changes may vary from one ventilator to another.

Humans↗

Expiratory tidal volume displayed on Bird 8400 STi can exceed the preset tidal volume due to cardiogenic oscillation: a lung model study.

We noticed that monitored tidal volumes often exceeded preset tidal volumes in patients with large cardiogenic oscillation. To investigate whether triggering modes affect this discrepancy, we simulated cardiogenic oscillation of 90 breaths/min in a lung model, which was ventilated with a Bird 8400 STi ventilator (Bird, Palm Springs, CA, USA). The magnitude of cardiogenic oscillation was defined as peak expiratory flow fluctuation at the lung model. Two respiratory rates (5 and 10 breaths/min) and two triggering modes (flow-triggering and pressure-triggering) were applied, while tidal volume was set at 500 ml. We recorded tidal volume on a ventilator monitor and calculated the discrepancy from the set tidal volume. We also measured fluctuation in flow and airway opening pressure created by cardiogenic oscillation. During flow-triggering, larger flow fluctuation and smaller airway pressure fluctuation were observed compared with during pressure-triggering. During flow-triggering, the discrepancy between monitored tidal volume and set value ranged from 0 to +327 ml at 5 breaths/min, and from 0 to +105 ml at 10 breaths/min. There was a linear correlation between the magnitude of cardiogenic oscillation and the overestimation of tidal volume. By contrast, during pressure-triggering, the discrepancy was small. In conclusion, tidal volume is overestimated during flow-triggering but not during pressure-triggering when cardiogenic oscillation is large.

Models, Biological↗

Effects of frequency, tidal volume, and lung volume on CO2 elimination in dogs by high frequency (2-30 Hz), low tidal volume ventilation.

Recent studies have shown that effective pulmonary ventilation is possible with tidal volumes (VT) less than the anatomic dead-space if the oscillatory frequency (f) is sufficiently large. We systematically studied the effect on pulmonary CO2 elimination (VCO2) of varying f (2-30 Hz) and VT (1-7 ml/kg) as well as lung volume (VL) in 13 anesthetized, paralyzed dogs in order to examine the contribution of those variables that are thought to be important in determining gas exchange by high frequency ventilation. All experiments were performed when the alveolar PCO2 was 40 +/- 1.5 mm Hg. In all studies, VCO2 increased monotonically with f at constant VT. We quantitated the effects of f and VT on VCO2 by using the dimensionless equation VCO2/VOSC = a(VT/VTo)b(f/fo)c where: VOSC = f X VT, VTo = mean VT, fo = mean f and a, b, c, are constants obtained by multiple regression. The mean values of a, b, and c for all dogs were 2.12 X 10(-3), 0.49, and 0.08, respectively. The most important variable in determining VCO2 was VOSC; however, there was considerable variability among dogs in the independent effect of VT and f on VCO2, with a doubling of VT at a constant VOSC causing changes in VCO2 ranging from -13 to +110% (mean = +35%). Increasing VL from functional residual capacity (FRC) to the lung volume at an airway opening minus body surface pressure of 25 cm H2O had no significant effect on VCO2.

Animals↗

Volume guarantee: stability of tidal volume and incidence of hypocarbia.

Excessive tidal volume (V(T)) can lead to lung injury, hypocarbia, and neurologic damage. Volume guarantee (VG) uses exhaled V(T) as the control variable to reduce the risk of volutrauma and more closely control PaCO(2). Our objective was to test the hypothesis that VG combined with assist/control (A/C) will maintain PaCO(2) and V(T) within target range more consistently than assist/control alone during the first 72 hr of life in ventilated preterm infants. Eligible infants were randomly assigned to A/C + VG or A/C alone. Data were recorded directly from the pressure and volume module of the Draeger Babylog 8000+ ventilator. Arterial blood gases were obtained every 2-6 hr, as clinically indicated. In A/C, inspiratory pressure was adjusted to achieve a V(T) of 4-6 ml/kg. In VG, the target V(T) was 5 ml/kg. Subsequent adjustments were made by the clinical team in response to arterial blood gas measurements (ABG). Proportion of breaths and PaCO(2) values outside the target range were compared by chi(2), and continuous variables by t-test. There were no differences in demographic or baseline ventilator variables between the 18 infants in the two groups. For 1,805/11,950 breaths (15.1%), V(T) was > target with A/C + VG, vs. 2,503/9,853 (25.4%) with A/C (P < 0.001). V(T) was < target for 21.7% of breaths with A/C + VG, vs. 35.7% with A/C (P < 0.001). Twenty percent of PaCO(2) values were < target, with A/C + VG vs. 36.3% with A/C, P < 0.05. The proportion of PaCO(2) values > target was similar in the two groups. Oxygenation and mean pH were not different. No complications related to mechanical ventilation were observed. In conclusion, VG significantly reduced hypocarbia and excessively large V(T). This suggests the potential to reduce pulmonary and neurologic complications of mechanical ventilation. Larger studies are needed to establish safety and demonstrate such benefits.

Carbon Dioxide↗

Correlation properties of tidal volume and end-tidal O2 and CO2 concentrations in healthy infants.

We investigated whether breath-to-breath fluctuations in tidal volume (VT) and end-tidal O2 and CO2 exhibit long-range correlations and whether parameters describing the correlations can be used as noninvasive descriptors of control of breathing. We measured VT and end-tidal O2 and CO2 over n = 352 +/- 104 breaths in 26 term, healthy, unsedated infants (mean age +/- SD: 36 +/- 6 days) and calculated the detrended fluctuation function [F(n)]. The F(n) of the breath-to-breath time series of VT, O2, and CO2 revealed a linear increase with a breath number on log-log plots with a slope that was significantly different from 0.5 (random) and thus consistent with scale-invariant behavior. Long-range correlations were stronger for O2 than for VT and CO2. The F(n) of many individual signals exhibited a crossover behavior indicating that control mechanisms regulating fluctuations of VT, O2, and CO2 may be different on different time scales. Thus breathing has a memory up to at least 400 breaths that can be characterized by the simple indicator alpha.

Carbon Dioxide↗

Effect of tidal volume and frequency on airway responsiveness in mechanically ventilated rabbits.

We evaluated the effects of the rate and volume of tidal ventilation on airway resistance (Raw) during intravenous methacholine (MCh) challenge in mechanically ventilated rabbits. Five rabbits were challenged at tidal volumes of 5, 10, and 20 ml/kg at a frequency of 15 breaths/min and also under static conditions (0 ml/kg tidal volume). Four rabbits were subjected to MCh challenge at frequencies of 6 and 30 breaths/min with a tidal volume of 10 ml/kg and also under static conditions. In both groups, the increase in Raw with MCh challenge was significantly greater under static conditions than during tidal ventilation at any frequency or volume. Increases in the volume or frequency of tidal ventilation resulted in significant decreases in Raw in response to MCh. We conclude that tidal breathing suppresses airway responsiveness in rabbits in vivo. The suppression of narrowing in response to MCh increases as the magnitude of the volume or the frequency of the tidal oscillations is increased. Our findings suggest that the effect of lung volume changes on airway responsiveness in vivo is primarily related to the stretch of airway smooth muscle.

Air Pressure↗

Tidal volume reduction for prevention of ventilator-induced lung injury in acute respiratory distress syndrome. The Multicenter Trail Group on Tidal Volume reduction in ARDS.

Because animal studies have demonstrated that mechanical ventilation at high volume and pressure can be deleterious to the lungs, limitation of airway pressure, allowing hypercapnia if necessary, is already used for ventilation of acute respiratory distress syndrome (ARDS). Whether a systematic and more drastic reduction is necessary is debatable. A multicenter randomized study was undertaken to compare a strategy aimed at limiting the end-inspiratory plateau pressure to 25 cm H2O, using tidal volume (VT) below 10 ml/kg of body weight, versus a more conventional ventilatory approach (with regard to current practice) using VT at 10 ml/kg or above and close to normal PaCO2. Both arms used a similar level of positive end-expiratory pressure. A total of 116 patients with ARDS and no organ failure other than the lung were enrolled over 32 mo in 25 centers. The two groups were similar at inclusion. Patients in the two arms were ventilated with different VT (7.1 +/- 1.3 versus 10.3 +/- 1.7 ml/kg at Day 1, p < 0.001) and plateau pressures (25.7 +/- 5. 0 versus 31.7 +/- 6.6 cm H2O at Day 1, p < 0.001), resulting in different PaCO2 (59.5 +/- 15.0 versus 41.3 +/- 7.6 mm Hg, p < 0.001) and pH (7.28 +/- 0.09 versus 7.4 +/- 0.09, p < 0.001), but a similar level of oxygenation. The new approach did not reduce mortality at Day 60 (46.6% versus 37.9% in control subjects, p = 0.38), the duration of mechanical ventilation (23.1 +/- 20.2 versus 21.4 +/- 16. 3 d, p = 0.85), the incidence of pneumothorax (14% versus 12%, p = 0. 78), or the secondary occurrence of multiple organ failure (41% versus 41%, p = 1). We conclude that no benefit could be observed with reduced VT titrated to reach plateau pressures around 25 cm H2O compared with a more conventional approach in which normocapnia was achieved with plateau pressures already below 35 cm H2O.

Adolescent↗

Patient-ventilator interactions during volume-support ventilation: asynchrony and tidal volume instability--a report of three cases.

During pressure-support ventilation, tidal volume (V(T)) can vary according to the level of the patient's respiratory effort and modifications of the thoraco-pulmonary mechanics. To keep V(T) as constant as possible, the Siemens Servo 300 ventilator proposes an original modification of pressure-support ventilation, called volume-support ventilation (VSV). VSV is a pressure-limited mode of ventilation that uses V(T) as a feedback control: the pressure support level is continuously adjusted to deliver a preset V(T). Thus, the ventilator adapts the inspiratory pressure level, breath by breath, to changes in the patient's inspiratory effort and the mechanical thoraco-pulmonary properties. The clinician sets V(T) and respiratory frequency, and the ventilator calculates a preset minute volume. It has been shown that ineffective respiratory efforts can occur during pressure-support ventilation.

Female↗

Effect of perfluorocarbon (perfluorooctyl bromide) vapor on tidal volume measurement during partial liquid ventilation.

OBJECTIVE: To compare measured tidal volumes with and without perfluorocarbon (perfluorooctyl bromide) vapor, by using tidal volumes in the range suitable for neonates ventilated with partial liquid ventilation. We also aimed to determine the correction factor needed to calculate tidal volumes measured in the presence of perfluorooctyl bromide vapor. DESIGN: Prospective, experimental study. SETTING: Neonatal research laboratory. INTERVENTIONS: Reproducible tidal volumes from 5 to 30 mL were produced with a rodent ventilator and drawn from humidifier chambers immersed in a water bath at 37 degrees C. Control tidal volumes were drawn from a chamber containing oxygen and water vapor, and the perfluorocarbon tidal volumes were drawn from a chamber containing oxygen, water vapor, and perfluorooctyl bromide vapor. MEASUREMENTS AND MAIN RESULTS: Tidal volumes were measured by a VenTrak respiratory mechanics monitor with a neonatal flow sensor and a Dräger pneumotachometer attached to a Dräger neonatal ventilator. All tidal volumes measured with perfluorooctyl bromide vapor were increased compared with control. The VenTrak-measured tidal volumes increased by 1.8% to 3.5% (an overall increase of 2.2%). The increase was greater with the Dräger hot-wire anemometer: from 2.4% to 6.1% (an overall increase of 5.9%). Regression equations for mean control tidal volumes (response, Y) vs. mean perfluorooctyl bromide tidal volumes (predictor, X) are as follows: for the VenTrak, Y = -0.026 + (0.978 x X), r =.9999, p <.0001; and for the Dräger, Y = 0.251 + (0.944 x X), r =.9996, p <.0001. CONCLUSIONS: The presence of perfluorooctyl bromide vapor in the gas flowing through pneumotachometers gives falsely high tidal volume measurements. An estimate of the true tidal volume allowing for the presence of perfluorooctyl bromide vapor can be made from regression equations. Any calculation of lung mechanics must take into account the effect of perfluorooctyl bromide vapor on the measurement of tidal volume.

Fluorocarbons↗

Pulse pressure variations to predict fluid responsiveness: influence of tidal volume.

OBJECTIVE: To evaluate the influence of tidal volume on the capacity of pulse pressure variation (DeltaPP) to predict fluid responsiveness. DESIGN: Prospective interventional study. SETTING: A 31-bed university hospital medico-surgical ICU. PATIENTS AND PARTICIPANTS: Sixty mechanically ventilated critically ill patients requiring fluid challenge, separated according to their tidal volume. INTERVENTION: Fluid challenge with either 1,000 ml crystalloids or 500 ml colloids. MEASUREMENTS AND RESULTS: Complete hemodynamic measurements including DeltaPP were obtained before and after fluid challenge. Tidal volume was lower than 7 ml/kg in 26 patients, between 7-8 ml/kg in 9 patients, and greater than 8 ml/kg in 27 patients. ROC curve analysis was used to evaluate the predictive value of DeltaPP at different tidal volume thresholds, and 8 ml/kg best identified different behaviors. Overall, the cardiac index increased from 2.66 (2.00-3.47) to 3.04 (2.44-3.96) l/min m(2) ( P <0.001). It increased by more than 15% in 33 patients (fluid responders). Pulmonary artery occluded pressure was lower and DeltaPP higher in responders than in non-responders, but fluid responsiveness was better predicted with DeltaPP (ROC curve area 0.76+/-0.06) than with pulmonary artery occluded pressure (0.71+/-0.07) and right atrial (0.56+/-0.08) pressures. Despite similar response to fluid challenge in low (<8 ml/kg) and high tidal volume groups, the percent of correct classification of a 12% DeltaPP was 51% in the low tidal volume group and 88% in the high tidal volume group. CONCLUSIONS: DeltaPP is a reliable predictor of fluid responsiveness in mechanically ventilated patients only when tidal volume is at least 8 ml/kg.

Aged↗