VT Ventilation Research Articles

Automated Alerting and Recommendations for the Management of Patients with Preexisting Hypoxia and Potential Acute Lung Injury

Acute lung injury (ALI) is associated with high mortality. Low tidal volume (Vt) ventilation has been shown to reduce mortality in ALI patients in the intensive care unit. Anesthesiologists do not routinely provide lung-protective ventilation strategies to patients with ALI in the operating room. The authors hypothesized that an alert, recommending lung-protective ventilation regarding patients with potential ALI, would result in lower Vt administration. The authors conducted a randomized controlled trial on anesthesia providers caring for patients with potential ALI. Patients with an average or last collected ratio of partial pressure of arterial oxygen to inspired fraction of oxygen less than 300 were randomized to providers being sent an alert with a recommended Vt of 6 cc/kg predicted body weight or conventional care. Primary outcomes were Vt/kg predicted body weight administered to patients. Secondary outcomes included ventilator parameters, length of postoperative ventilation, and death. The primary outcome was a clinically significant reduction in mean Vt from 508-458 cc (P = 0.033), with a reduction in Vt when measured in cc/kg predicted body weight from 8 to 7.2 cc/kg predicted body weight (P = 0.040). There were no statistically significant changes in other outcomes or adverse events associated with either arm. Automated alerts generated for patients at risk of having ALI resulted in a statistically significant reduction in Vt administered when compared with a control group. Further research is required to determine whether a reduction in Vt results in decreased mortality and/or postoperative duration of mechanical ventilation.

Effect of protective ventilation on organ-specific cytokine production in an experimental postoperative sepsis model

Low tidal volume (VT) ventilation in intensive care patients without lung injury attenuates the systemic inflammatory response [1]. The contribution of the specific organ inflammatory responses to the systemic picture remains to be elucidated. We investigated the effect of low VT ventilation compared with medium high VT on hepatic, splanchnic and cerebral cytokine responses in an experimental large animal postoperative sepsis model.

The effects of mechanical ventilation with different tidal volumes on the expression of caveolin-1 in lung tissue and its related downstream signaling in rats

To investigate the expression of caveolin-1 (cav-1) and its downstream signal under mechanical ventilation with different tidal volumes (VT) in lung tissue of rats. Forty healthy male Sprague-Dawley (SD) rats were randomly assigned into five groups (each n=8). The rats in control group (group A) remained to have spontaneous breathing but underwent tracheostomy only. The rats in protective ventilation group underwent protective ventilation for 1 hour or 2 hours (group B1, B2), with VT set at 6 ml/kg. The rats in high VT ventilation group were given mechanical ventilation for 1 hour or 2 hours (group C1, C2), with VT set at 30 ml/kg. After incision of trachea in group A, and mechanical ventilation was given for 1 hour or 2 hours in ventilation groups. Rats of group A were sacrificed immediately. Rats of other groups were sacrificed 1 hour or 2 hours after mechanical ventilation. Specimens of lung tissues and bronchoalveolar lavage fluid (BALF) were harvested. Lung pathological changes were observed with optical microscope. The expression levels of cav-1 mRNA and eNOS mRNA in lung tissue were measured by reverse transcription-polymerase chain reaction (RT-PCR). The protein levels of cav-1, endothelial nitric oxide synthase (eNOS), interleukin-1 receptor-associated kinase 4 (IRAK4) and nuclear factor-ΚB (NF-ΚB) p65 in lung tissues were assayed with immunohistochemistry staining. Lung myeloperoxidase (MPO) activity was measured by colorimetric analysis, and wet/dry weight ratio (W/D) was calculated. The levels of tumor necrosis factor-α (TNF-α) in BALF was measured by enzyme-linked immunosorbent assay (ELISA). No statistical significance in the mRNA expression of cav-1 and eNOS, the protein expression of cav-1, eNOS, IRAK4, NF-ΚBp65, as well as W/D ratio, MPO and TNF-α in BALF was found among group A, group B1 and group B2. The expression of cav-1 mRNA (A value ratio) and cav-1, IRAK4, NF-ΚBp65 protein (A value) were significantly up-regulated (cav-1 mRNA: 0.833±0.085 vs. 0.384±0.011, 1.162±0.166 vs. 0.388±0.014; cav-1 protein: 0.188±0.011 vs. 0.140±0.052, 0.210±0.013 vs. 0.125±0.014; IRAK4 protein: 0.181±0.009 vs. 0.150±0.008, 0.205±0.085 vs. 0.155±0.012;NF-ΚBp65 protein: 0.294±0.011 vs. 0.236±0.015, 0.304±0.012 vs. 0.239±0.005), the expression of eNOS mRNA (A value ratio) and protein (A value) was significantly down-regulated (eNOS mRNA: 0.174±0.016 vs. 0.278±0.021, 0.107±0.014 vs. 0.262±0.045; eNOS protein: 0.180±0.017 vs. 0.211±0.010, 0.161±0.016 vs. 0.216±0.013), while W/D ratio, MPO and TNF-α in BALF were significantly increased (W/D: 5.64±0.42 vs. 4.63±0.12, 6.73±0.83 vs. 4.70±0.15; MPO: 1.86±0.26 U/g vs. 0.85±0.11 U/g, 2.14±0.24 U/g vs. 0.88±0.18 U/g; TNF-α: 386.53±29.12 ng/L vs. 50.57±10.98 ng/L, 455.77±37.78 ng/L vs. 52.11±9.92 ng/L) in group C1 and group C2 compared with those in group B1 and group B2 (all P<0.05). With prolongation of time of mechanical ventilation, changes in those parameters were more obvious in group C2 as compared with group C1 (all P<0.05). Cav-1 and the activation of downstream signals in lung tissue participate in the development of the ventilator-induced lung injury.

Effect of lung protection mechanical ventilation on respiratory function in the elderly undergoing spinal fusion

To determine the effect of lung protection mechanical ventilation on respiratory function in the elderly undergoing spinal fusion. Sixty 70-85 year old patients, ASA class II or III, undergoing spinal fusion were randomly assigned into 2 groups (30 in each group): a protection mechanical ventilation group (group P) and a conventional mechanical ventilation group (group C). Low VT and low level positive end expiratory pressure (PEEP) mechanical ventilation were applied in group P (VT=6mL/kg, RR=12-18 b/min, I:E=1:2, PEEP=10 cmH2O, alveolar recruitment performed once every 15 min), while traditional ventilation was used in group C ( VT=10-12 mL/kg, RR=12 b/min, I:E=1:2). Arterial blood samples were taken and pH, PaO2, PaCO2, PaO2/FiO2, A-aDO2, HR, SBP, DBP and CVP were recorded before the operation (T0), 1 h after tracheal intubation (T1), tracheal extubation immediately (T2), 1 h after tracheal extubation (T3), 1 d, 2 d, and 3 d after the operation (T4, T5, and T6). The pulmonary complication was also examined 1 d after the operation. At T1, T2, T3, T4 and T5, PaO2 and PaO2/FiO2 in group P were higher than those in group C, but A-aDO2 in group P was lower than that in group C. Five patients had bronchitis, 5 had hyoxemia, and 3 had atelectasis in group C, but 2 bronchitis in group P. The incidence of pulmonary complication was 43.3% in group C and 6.6% in group P. There was no significant difference in HR, SBP, DBP and CVP between the 2 groups. Lung protection mechanical ventilation improves the arterial oxygenation and accelerates the recovery of respiratory functions in elderly patients after spinal fusion operation, with no influence on hemodynamics.

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Introduction: This study sought to determine if TeleICU directed daily ventilator rounds led to improved adherence to low tidal volume(Vt) ventilation, reduced (APACHE IV adjusted) Ventilator Duration Ratio (VDR),ICU and hospital mortality ratio, and ICU LOS. Hypothesis: We hypothesized that TeleICU directed process improvement initiatives could improve outcomes across disparate practice. Methods: Nine community hospital ICUs participating in TeleICU directed daily structured ventilator rounds were enrolled in this retrospective longitudinal quarterly analysis of adherence to low Vt strategy(<7.5ml/kg IBW for P/F<300), VDR, ICU and hospital mortality ratios, and ICU LOS. The independent TeleICU practice utilized Philips VISICU licensed eCare Manager(tm) platform, providing ICU care and process improvement. Data were extracted from the proprietary database. Ventilator rounds were led byTeleICU physicians using audiovisual links to patients, bedside RTs and RNs. Ventilator settings, ABG, CXR and liberation readiness parameters were pre-entered into an electronic spreadsheet by TeleICU CCRNs and NPs. Results: Prior to ventilator rounds implementation there was wide variation in hospital adherence to low Vt strategy [mean 26%; SD 18.4;range 13-69%]. Significant quarterly improvement was seen in all hospitals after implementation [32.6, 43.2 and 42% Q1,2,3; p<0.001 by two tail Fisher exact test]. VDR also showed pre-implementation variability [mean 1.16;SD 0.52; range 0.64-2.0] and showed improved trending throughout the study [quarterly VDR 0.89, 0.84 and 0.88; range 0.63-1.4; p=NS]. ICU mortality ratio demonstrated longitudinal improvement that reached significance after the second quarter post-implementation [0.94 pre- v. 0.8, 0.73 and 0.67 post-implementation; p<0.03 pre- v. Q2]. ICU LOS and hospital mortality ratio were not significantly changed. Conclusions: Variable practices among ICUs pose challenges to TeleICU led process improvement. Despite this, implementation of TeleICU ventilator rounds was associated with improved and durable adherence to low Vt strategies and significant reduction in mortality.

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Introduction: Low tidal volume (VT),6 ml/kg, has proved to reduce mortality in ALI/ ARDS, probably by reducing the extent of ventilation induced lung injury (VILI). A further reduction of VT may be advantageous. Indeed, ventilation with 3 ml/kg VT decreased the inflammatory response in patients with low lung compliance compared with 6 ml/kg. When using very low VTs the use of an extracorporeal CO2 removal to keep PaCO2 and thus a normal pH has been proposed. NaHCO3 has been used to normalize pH is this context, but experimental studies indicate that this could increase VILI. Hypothesis: THAM, a proton acceptor, could be a possible method to maintain an acceptable pH during very low VT ventilation. Methods: In 10 lung lavaged, anesthetized, muscle-relaxed pigs, normo-ventilated (pH 7,4 ± 0,01, PaCO2 45 ± 3 mmHg, Base excess (BE) 2,9 ± 1,6 mEq/L, M±SD) with a VT of 6 ml/kg,FIO2 1.0 and 10 cmH2O PEEP via a tracheal double lumen tube, VT was abruptly changed to 3 ml/kg, which was maintained for the rest of the 6 hours experiment. In 5 of the animals THAM (3 mmol/kg) was infused iv during the first hour, aiming at increasing BE by 10 mEq/L, while the other 5 animals served as controls. Results: After 1 hour, pH in the THAM group decreased to 7,33 ± 0,06, PaCO2 increased to 77 ± 7 mmHg, and BE increased to 13 ± 3,6 mEq/L, and in the controls pH decreased to 7,14 ± 0,04, PaCO2 increased to 96 ± 7 mmHg (p<0.001 and 0.003, between the groups, respectively),whereas no change occurred in BE. After 6 hours, pH and PaCO2 were similar in the THAM and control groups (7,19 ± 0,05 vs 7,13 ± 0,06 (p=0.056), and 106 ± 15 vs 105 ± 13 mmHg, resp), while BE was higher in the THAM group (10 ± 2,2 vs.4,0 ± 3,1 mEq/L in the control group,p=0.008).Hemodynamics was stable, but MPAP at 1 hour was lower in the THAM group (22 ± 3 vs. 28 ± 4 mmHg, p=0.04). No differences in PaO2, lung mechanics or functional residual capacity were found between the groups indicating that THAM did not increase VILI. Conclusions: In this pilot study, THAM had a short-term effect on pH but a long term effect on BE. This suggests that it may be feasible to use THAM at a somewhat higher dose than in this study when inducing extremely low VT ventilation to keep pH in an acceptable physiological range.

Control of breathing and blood pressure by parafacial neurons in conscious rats

The retrotrapezoid nucleus (RTN), located in the parafacial region, contains glutamatergic neurons that express the transcriptor factor Phox2b and that are suggested to be central respiratory chemoreceptors. Studies in anaesthetized animals or in vitro have suggested that RTN neurons are important in the control of breathing by influencing respiratory rate, inspiratory amplitude and active expiration. However, the contribution of these neurons to cardiorespiratory control in conscious rats is not clear. Male Holtzman rats (280-300 g, n = 6-8) with bilateral stainless-steel cannulae implanted into the RTN were used. In conscious rats, the microinjection of the ionotropic glutamatergic agonist NMDA (5 pmol in 50 nl) into the RTN increased respiratory frequency (by 42%), tidal volume (by 21%), ventilation (by 68%), peak expiratory flow (by 24%) and mean arterial pressure (MAP, increased by 16 ± 4, versus saline, 3 ± 2 mmHg). Bilateral inhibition of the RTN neurons with the GABA(A) agonist muscimol (100 pmol in 50 nl) reduced resting ventilation (52 ± 34, versus saline, 250 ± 56 ml min(-1) kg(-1) with absolute values) and attenuated the respiratory response to hypercapnia and hypoxia. Muscimol injected into the RTN slightly reduced resting MAP (decreased by 13 ± 7, versus saline, increased by 3 ± 2 mmHg), without changing the effects of hypercapnia or hypoxia on MAP and heart rate. The results suggest that RTN neurons activate facilitatory mechanisms important to the control of ventilation in resting, hypoxic or hypercapnic conditions in conscious rats.

Does a Protective Ventilation Strategy Reduce the Risk of Pulmonary Complications After Lung Cancer Surgery?: A Randomized Controlled Trial

Protective ventilation strategy has been shown to reduce ventilator-induced lung injury in patients with ARDS. In this study, we questioned whether protective ventilatory settings would attenuate lung impairment during one-lung ventilation (OLV) compared with conventional ventilation in patients undergoing lung resection surgery. One hundred patients with American Society of Anesthesiology physical status 1 to 2 who were scheduled for an elective lobectomy were enrolled in the study. During OLV, two different ventilation strategies were compared. The conventional strategy (CV group, n=50) consisted of FIO2 1.0, tidal volume (Vt) 10 mL/kg, zero end-expiratory pressure, and volume-controlled ventilation, whereas the protective strategy (PV group, n=50) consisted of FIO2 0.5, Vt 6 mL/kg, positive end-expiratory pressure 5 cm H2O, and pressure-controlled ventilation. The composite primary end point included PaO2/FIO2<300 mm Hg and/or the presence of newly developed lung lesions (lung infiltration and atelectasis) within 72 h of the operation. To monitor safety during OLV, oxygen saturation by pulse oximeter (SpO2), PaCO2, and peak inspiratory pressure (PIP) were repeatedly measured. During OLV, although 58% of the PV group needed elevated FIO2 to maintain an SpO2>95%, PIP was significantly lower than in the CV group, whereas the mean PaCO2 values remained at 35 to 40 mm Hg in both groups. Importantly, in the PV group, the incidence of the primary end point of pulmonary dysfunction was significantly lower than in the CV group (incidence of PaO2/FIO2<300 mm Hg, lung infiltration, or atelectasis: 4% vs 22%, P<.05). Compared with the traditional large Vt and volume-controlled ventilation, the application of small Vt and PEEP through pressure-controlled ventilation was associated with a lower incidence of postoperative lung dysfunction and satisfactory gas exchange. Australian New Zealand Clinical Trials Registry; No.: ACTRN12609000861257; URL: www.anzctr.org.au.

Inflammation and lung maturation from stretch injury in preterm fetal sheep.

Mechanical ventilation is a risk factor for the development of bronchopulmonary dysplasia in premature infants. Fifteen minutes of high tidal volume (V(T)) ventilation induces inflammatory cytokine expression in small airways and lung parenchyma within 3 h. Our objective was to describe the temporal progression of cytokine and maturation responses to lung injury in fetal sheep exposed to a defined 15-min stretch injury. After maternal anesthesia and hysterotomy, 129-day gestation fetal lambs (n = 7-8/group) had the head and chest exteriorized. Each fetus was intubated, and airway fluid was gently removed. While placental support was maintained, the fetus received ventilation with an escalating V(T) to 15 ml/kg without positive end-expiratory pressure (PEEP) for 15 min using heated, humidified 100% nitrogen. The fetus was then returned to the uterus for 1, 6, or 24 h. Control lambs received a PEEP of 2 cmH(2)O for 15 min. Tissue samples from the lung and systemic organs were evaluated. Stretch injury increased the early response gene Egr-1 and increased expression of pro- and anti-inflammatory cytokines within 1 h. The injury induced granulocyte/macrophage colony-stimulating factor mRNA and matured monocytes to alveolar macrophages by 24 h. The mRNA for the surfactant proteins A, B, and C increased in the lungs by 24 h. The airway epithelium demonstrated dynamic changes in heat shock protein 70 (HSP70) over time. Serum cortisol levels did not increase, and induction of systemic inflammation was minimal. We conclude that a brief period of high V(T) ventilation causes a proinflammatory cascade, a maturation of lung monocytic cells, and an induction of surfactant protein mRNA.

Lung fluid absorption is induced in preterm guinea pigs ventilated with low tidal volumes

ABSTRACTThe objective of this study was to determine if low tidal volume (Vt) ventilation was beneficial when ventilating preterm fetuses. The authors ventilated preterm guinea pig fetuses at gestation day (GD) 67, 3 days before birth, newborn, and 10-day-old (PD10) guinea pigs with low Vt (6 mL/kg body weight [bw]) and compared them to age-matched fetuses/animals ventilated with higher potentially injurious Vt (12 mL/kg bw). Lung fluid absorption was measured after intratracheal instillation of 5% albumin in 0.9% NaCl. Low Vt ventilation stimulated lung fluid absorption when compared to higher Vt in all groups. The increased lung fluid absorption in low Vt–ventilated fetuses was associated with increased α epithelial Na channel (αEnaC) mRNA. However, αENaC and βENaC protein was unchanged over the 1-hour study. Because stretch induces mitogen-activated protein (MAP) kinase expression and MAP kinases may affect lung fluid absorption, the authors investigated if MAP kinase (MAPK) expression was affected by Vt. Extracellular signal-regulated kinase (ERK) and MAPK/ERK kinase (MEK) were phosphorylated in the higher Vt–ventilated guinea pig fetuses. This suggested that a reduced activation of MAP kinases might explain the increased lung fluid absorption in the low Vt–ventilated fetuses. Thus these data suggest that low Vt ventilation increases fetal lung fluid absorption and thus may be preferential to use clinically.

Influence of Tidal Volume on Pulse Pressure Variations in Hypovolemic Ventilated Pigs with Acute Respiratory Distress-like Syndrome

Sensitivity and specificity of respiratory change in pulse pressure (DeltaPP) to predict preload dependency has been questioned at small tidal volumes (VT) in critically ill patients suffering from acute respiratory distress syndrome (ARDS). We studied DeltaPP in pigs with ARDS-like syndrome during reversible hemorrhagic shock. Prospective, observational animal study in a Laboratory Investigation Unit. Sixteen deeply sedated mechanically ventilated pigs were successively ventilated with VT of 10 ml/kg at a respiratory rate of 15 breaths/min (RR15) and VT of 6 ml/kg at RR15 and RR25. ARDS-like syndrome was produced by lung lavage in eight pigs (ARDS group). Severe hemorrhagic shock was induced by removal of 40% of total blood volume followed by restoration. After bleeding, in the control group ventilated with a VT of 10 ml/kg, DeltaPP increased from 8.5 (95% confidence interval [CI], 7.1 to 9.9%) to 18.5% (CI, 15.3 to 21.7%; P<0.05). In the ARDS group, this index increased similarly, from 7.1% (95% CI, 5.3 to 9.0%) to 20.1% (CI, 15.3 to 24.9%; P<0.05). In control lungs, reduction in VT from 10 to 6 ml/kg reduced the DeltaPP reaction by 40%, although it remained a statistically valid indicator of hypovolemia regardless of the RR value. In contrast, in the ARDS group, DeltaPP was an unreliable hypovolemia marker at low VT ventilation, regardless of the RR value (p=not statistically significant). The present study suggests that DeltaPP is a reliable indicator of severe hypovolemia in pigs with healthy lungs regardless of VT or RR. In contrast, in pigs with ARDS-like syndrome ventilated with small VT, DeltaPP is not a good indicator of severe hemorrhage. However, in this setting, indexing DeltaPP to respiratory changes in transpulmonary pressure allows this marker to significantly indicate the occurrence of hypovolemia.

Ventilation-Mediated Injury After Preterm Delivery of Ureaplasma parvum Colonized Fetal Lambs

Ureaplasma species are the microorganisms most frequently isolated from women with preterm birth and are associated with an increased risk of bronchopulmonary dysplasia. Initiation of ventilation with high tidal volumes (VT) causes lung injury and inflammation. We investigated whether antenatal colonization with Ureaplasma parvum serovar 3 (UP) would alter the inflammatory response to mechanical ventilation of preterm lambs. Merino ewes were given intraamniotic injections of UP at 55-d gestation, and the lambs were surgically delivered at 128+/-1 d gestation and assigned to three groups: 1) gentle ventilation (GV), 2) high VT ventilation, or 3) unventilated control. Lambs delivered from noncolonized ewes were assigned to parallel groups. GV lambs received surfactant before ventilation with a VT of 7 mL/kg, positive end expiratory pressure (PEEP) 5 cm H2O. High VT lambs received no PEEP and escalating VT to 15 mL/kg by 15 min. At 15 min, surfactant was given, VT was reduced to 7 mL/kg, and PEEP was increased to 5 cm H2O. Monocytes in bronchoalveolar lavage were increased by UP, but colonization did not affect lung function. High VT ventilation increased Egr-1 signaling, proinflammatory cytokine expression, and injury scores compared with GV. Antenatal colonization with UP did not change lung function or modulate the lung injury and inflammation caused by high VT ventilation.

Effect of different tidal volume ventilation on apoptosis and the expression of Bax and Bcl-2 in rat lungs

To determine the effect of different tidal volume(Vt) ventilation on apoptosis and the expression of Bax and Bcl-2 in rat lungs. Twenty-four healthy SD rats were randomly divided into 4 groups: a control group, a low Vt ventilation group (LV), a middle Vt ventilation group (MV), and a high Vt ventilation group (HV). Rats were subjected to different tidal volumes (10,20,and 40 mL/kg) for 2 h except the control group, which kept their own breath. We determined the lung histopathology score, W/D ratio and WBC in bronchoalceolar lavage fluid (BALF) to evaluate the lung injury and examine the apoptotic cell death, Bax and Bcl-2 protein expression by using TUNEL technique and immunohistochemistry 24 h after the operation. Compared with the control group, MV and HV increased lung histopathology score, W/D ratio, WBC in BALF, apoptosis index (AI )and Bax protein expression, but decreased Bcl-2 protein expression (P<0.05). These changes showed no significant difference between the control group and the low Vt ventilation group (P>0.05). Low Vt ventilation contributed little to apoptosis. Higher Vt ventilation can improve Bax while inhibit Bcl-2 expression to aggravate apoptosis in rat lungs.

Increased cardiac microvascular permeability and activation of cardiac endothelial nitric oxide synthase in high tidal volume ventilation-induced lung injury

Abstract Background: Positive pressure ventilation with large tidal volumes has been shown to cause lung injury via the serine/threonine kinase-protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS)-pathways. However, the effects of high tidal volume (VT) ventilation on the heart are unclear. Objectives: Evaluate the effect of VT ventilation on the cardiac vascular permeability and intracellular Akt and eNOS signaling pathway. Methods: C57BL/6 and Akt knock-out (heterozygotes, +/−) mice were exposed to high VT (30 mL/kg) mechanical ventilation with room air for one and/or five hours. Results: High VT ventilation increased cardiac microvascular permeability and eNOS phosphorylation in a timedependent manner. Serum cardiac troponin I was increased after one hour of high VT ventilation. Cardiac Akt phosphorylation was accentuated after one hour and attenuated after five hours of high VT ventilation. Pharmacological inhibition of Akt with LY294002 and high VT ventilation of Akt+/− mice attenuated cardiac Akt phosphorylation, but not eNOS phosphorylation. Conclusion: High VT ventilation increased cardiac myocardial injury, microvascular permeability, and eNOS phosphorylation. Involvement of cardiac Akt in high VT ventilation was transient.

Antenatal and postnatal corticosteroid and resuscitation induced lung injury in preterm sheep

BackgroundInitiation of ventilation using high tidal volumes in preterm lambs causes lung injury and inflammation. Antenatal corticosteroids mature the lungs of preterm infants and postnatal corticosteroids are used to treat bronchopulmonary dysplasia.ObjectiveTo test if antenatal or postnatal corticosteroids would decrease resuscitation induced lung injury.Methods129 d gestational age lambs (n = 5-8/gp; term = 150 d) were operatively delivered and ventilated after exposure to either 1) no medication, 2) antenatal maternal IM Betamethasone 0.5 mg/kg 24 h prior to delivery, 3) 0.5 mg/kg Dexamethasone IV at delivery or 4) Cortisol 2 mg/kg IV at delivery. Lambs then were ventilated with no PEEP and escalating tidal volumes (VT) to 15 mL/kg for 15 min and then given surfactant. The lambs were ventilated with VT 8 mL/kg and PEEP 5 cmH20 for 2 h 45 min.ResultsHigh VT ventilation caused a deterioration of lung physiology, lung inflammation and injury. Antenatal betamethasone improved ventilation, decreased inflammatory cytokine mRNA expression and alveolar protein leak, but did not prevent neutrophil influx. Postnatal dexamethasone decreased pro-inflammatory cytokine expression, but had no beneficial effect on ventilation, and postnatal cortisol had no effect. Ventilation increased liver serum amyloid mRNA expression, which was unaffected by corticosteroids.ConclusionsAntenatal betamethasone decreased lung injury without decreasing lung inflammatory cells or systemic acute phase responses. Postnatal dexamethasone or cortisol, at the doses tested, did not have important effects on lung function or injury, suggesting that corticosteroids given at birth will not decrease resuscitation mediated injury.

Meta-analysis: Ventilation Strategies and Outcomes of the Acute Respiratory Distress Syndrome and Acute Lung Injury

Trials have provided conflicting results regarding the effect of different ventilatory strategies on the outcomes of patients with the acute respiratory distress syndrome (ARDS) and acute lung injury. To determine whether ventilation with low tidal volume (Vt) and limited airway pressure or higher positive end-expiratory pressure (PEEP) improves outcomes for patients with ARDS or acute lung injury. Multiple computerized databases (through March 2009), reference lists of identified articles, and queries of principal investigators. No language restrictions were applied. Randomized, controlled trials (RCTs) reporting mortality and comparing lower versus higher Vt ventilation, lower versus higher PEEP, or a combination of both in adults with ARDS or acute lung injury. Using a standard protocol, 2 reviewer teams assessed trial eligibility and abstracted data on quality of study design and conduct, population characteristics, intervention, co-interventions, and confounding variables. 4 RCTs tested lower versus higher Vt ventilation at similar PEEP in 1149 patients, 3 RCTs compared lower versus higher PEEP at low Vt ventilation in 2299 patients, and 2 RCTs compared a combination of higher Vt and lower PEEP ventilation versus lower Vt and higher PEEP ventilation in 148 patients. Lower Vt ventilation reduced hospital mortality (odds ratio, 0.75 [95% CI, 0.58 to 0.96]; P = 0.02) compared with higher Vt ventilation at similar PEEP. Higher PEEP did not reduce hospital mortality (odds ratio, 0.86 [CI, 0.72 to 1.02]; P = 0.08) compared with lower PEEP using low Vt ventilation. Higher PEEP reduced the need for rescue therapy to prevent life-threatening hypoxemia (odds ratio, 0.51 [CI, 0.36 to 0.71]; P < 0.001) and death (odds ratio, 0.51 [CI, 0.36 to 0.71]; P < 0.001) in patients receiving rescue therapies. Pooling according to similar ventilatory strategies resulted in few RCTs analyzed in each group. The benefit of low Vt is derived from only 1 study. Available evidence from a limited number of RCTs shows better outcomes with routine use of low Vt but not high PEEP ventilation in unselected patients with ARDS or acute lung injury. High PEEP may help to prevent life-threatening hypoxemia in selected patients.

Tidal Volume Lower than 6 ml/kg Enhances Lung Protection

Tidal hyperinflation may occur in patients with acute respiratory distress syndrome who are ventilated with a tidal volume (VT) of 6 ml/kg of predicted body weight develop a plateau pressure (PPLAT) of 28 < or = PPLAT < or = 30 cm H2O. The authors verified whether VT lower than 6 ml/kg may enhance lung protection and that consequent respiratory acidosis may be managed by extracorporeal carbon dioxide removal. PPLAT, lung morphology computed tomography, and pulmonary inflammatory cytokines (bronchoalveolar lavage) were assessed in 32 patients ventilated with a VT of 6 ml/kg. Data are provided as mean +/- SD or median and interquartile (25th and 75th percentile) range. In patients with 28 < or = PPLAT < or = 30 cm H2O (n = 10), VT was reduced from 6.3 +/- 0.2 to 4.2 +/- 0.3 ml/kg, and PPLAT decreased from 29.1 +/- 1.2 to 25.0 +/- 1.2 cm H2O (P < 0.001); consequent respiratory acidosis (Paco2 from 48.4 +/- 8.7 to 73.6 +/- 11.1 mmHg and pH from 7.36 +/- 0.03 to 7.20 +/- 0.02; P < 0.001) was managed by extracorporeal carbon dioxide removal. Lung function, morphology, and pulmonary inflammatory cytokines were also assessed after 72 h. Extracorporeal assist normalized Paco2 (50.4 +/- 8.2 mmHg) and pH (7.32 +/- 0.03) and allowed use of VT lower than 6 ml/kg for 144 (84-168) h. The improvement of morphological markers of lung protection and the reduction of pulmonary cytokines concentration (P < 0.01) were observed after 72 h of ventilation with VT lower than 6 ml/kg. No patient-related complications were observed. VT lower than 6 ml/Kg enhanced lung protection. Respiratory acidosis consequent to low VT ventilation was safely and efficiently managed by extracorporeal carbon dioxide removal.

HIGH-TIDAL VOLUME VENTILATION AGGRAVATES SEPSIS-INDUCED MULTIORGAN DYSFUNCTION IN A DEXAMETHASONE-INHIBITABLE MANNER

High-tidal volume (Vt) ventilation induces lung injury and systemic inflammation, and small doses of endotoxin have been shown to increase the susceptibility to ventilation-induced lung injury. We studied whether high-Vt ventilation increases organ injury in a model of bacterial sepsis and whether an anti-inflammatory treatment averts those changes. Anesthetized rats, monitored with an arterial catheter and a blood flow probe in the aorta, were assigned to one of four different groups: nonseptic low-Vt group (Vt = 9 mL/kg, positive end-expiratory pressure = 8 cm H2O, control group), septic low-Vt group, septic overventilated group (Vt = 35 mL/kg, positive end-expiratory pressure = 0), and septic overventilated group pretreated with dexamethasone (6 mg/kg i.p., 30 min before mechanical ventilation). Rats were ventilated for 75 min. Septic rats had undergone cecal ligation and puncture 48 h before mechanical ventilation. We measured hemodynamics, lung mechanics, blood chemistry and gas exchange, liver and heart expression of cyclooxygenase 2 (COX-2) and iNOS (reverse transcriptase-polymerase chain reaction), and lung histopathology. Septic rats showed metabolic acidosis, hyperlactatemia, lung and liver injury, increased liver and heart COX-2, and liver iNOS expression. High-Vt ventilation of septic rats was associated with more marked liver injury and heart COX-2 upregulation, as well as lung inflammation and dysfunction (impaired oxygenation, increased bronchoalveolar lavage fluid protein and IL-6 concentration, decreased thoracic system compliance) and systemic hypotension. All inflammatory changes, as well as pulmonary and vascular dysfunctions, were abrogated by dexamethasone. High-Vt ventilation in bacterial sepsis upregulates the inflammatory response and aggravates the sepsis-induced cardiovascular, pulmonary, and liver dysfunction. Dexamethasone averts mechanical ventilation-induced changes under conditions of bacterial sepsis.

Pulmonary atelectasis during low stretch ventilation: “Open lung” versus “lung rest” strategy*

Limiting tidal volume (VT) may minimize ventilator-induced lung injury (VILI). However, atelectasis induced by low VT ventilation may cause ultrastructural evidence of cell disruption. Apoptosis seems to be involved as protective mechanisms from VILI through the involvement of mitogen-activated protein kinases (MAPKs). We examined the hypothesis that atelectasis may influence the response to protective ventilation through MAPKs. Prospective randomized study. University animal laboratory. Adult male 129/Sv mice. Isolated, nonperfused lungs were randomized to VILI: VT of 20 mL/kg and positive end-expiratory pressure (PEEP) zero; low stretch/lung rest: VT of 6 mL/kg and 8-10 cm H2O of PEEP; low stretch/open lung: VT of 6 mL/kg, two recruitment maneuvers and 14-16 cm H2O of PEEP. Ventilator settings were adjusted using the stress index. Both low stretch strategies equally blunted the VILI-induced derangement of respiratory mechanics (static volume-pressure curve), lung histology (hematoxylin and eosin), and inflammatory mediators (interleukin-6, macrophage inflammatory protein-2 [enzyme-linked immunosorbent assay], and inhibitor of nuclear factor-kB[Western blot]). VILI caused nuclear swelling and membrane disruption of pulmonary cells (electron microscopy). Few pulmonary cells with chromatin condensation and fragmentation were seen during both low stretch strategies. However, although cell thickness during low stretch/open lung was uniform, low stretch/lung rest demonstrated thickening of epithelial cells and plasma membrane bleb formation. Compared with the low stretch/open lung, low stretch/lung rest caused a significant decrease in apoptotic cells (terminal deoxynucleotidyl transferase mediated deoxyuridine-triphosphatase nick end-labeling) and tissue expression of caspase-3 (Western blot). Both low stretch strategies attenuated the activation of MAPKs. Such reduction was larger during low stretch/open lung than during low stretch/lung rest (p < 0.001). Low stretch strategies provide similar attenuation of VILI. However, low stretch/lung rest strategy is associated to less apoptosis and more ultrastructural evidence of cell damage possibly through MAPKs-mediated pathway.

Risk Factors for ARDS in Patients Receiving Mechanical Ventilation for > 48 h

Low tidal volume (Vt) ventilation for ARDS is a well-accepted concept. However, controversy persists regarding the optimal ventilator settings for patients without ARDS receiving mechanical ventilation. This study tested the hypothesis that ventilator settings influence the development of new ARDS. Retrospective analysis of patients from the Multi Parameter Intelligent Monitoring of Intensive Care-II project database who received mechanical ventilation for > or = 48 h between 2001 and 2005. A total of 2,583 patients required > 48 h of ventilation. Of 789 patients who did not have ARDS at hospital admission, ARDS developed in 152 patients (19%). Univariate analysis revealed high peak inspiratory pressure (odds ratio [OR], 1.53 per SD; 95% confidence interval [CI], 1.28 to 1.84), increasing positive end-expiratory pressure (OR, 1.35 per SD; 95% CI, 1.15 to 1.58), and Vt (OR, 1.36 per SD; 95% CI, 1.12 to 1.64) to be significant risk factors. Major nonventilator risk factors for ARDS included sepsis, low pH, elevated lactate, low albumin, transfusion of packed RBCs, transfusion of plasma, high net fluid balance, and low respiratory compliance. Multivariable logistic regression showed that peak pressure (OR, 1.31 per SD; 95% CI, 1.08 to 1.59), high net fluid balance (OR, 1.3 per SD; 95% CI, 1.09 to 1.56), transfusion of plasma (OR, 1.26 per SD; 95% CI, 1.07 to 1.49), sepsis (OR, 1.57; 95% CI, 1.00 to 2.45), and Vt (OR, 1.29 per SD; 95% CI, 1.02 to 1.52) were significantly associated with the development of ARDS. The associations between the development of ARDS and clinical interventions, including high airway pressures, high Vt, positive fluid balance, and transfusion of blood products, suggests that ARDS may be a preventable complication in some cases.