Predictors of mortality in acute lung injury during the era of lung protective ventilation.

BACKGROUND: Lung protective ventilation has been widely adopted for the management of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Consequently, ventilator associated lung injury and mortality have decreased. It is not known if this ventilation strategy changes the prognostic value of previously identified demographic and pulmonary predictors of mortality, such as respiratory compliance and the arterial oxygen tension to inspired oxygen fraction ratio (Pao(2)/Fio(2)). METHODS: Demographic, clinical, laboratory and pulmonary variables were recorded in 149 patients with ALI/ARDS. Significant predictors of mortality were identified in bivariate analysis and these were entered into multivariate analysis to identify independent predictors of mortality. RESULTS: Hospital mortality was 41%. In the bivariate analysis, 17 variables were significantly correlated with mortality, including age, APACHE II score and the presence of cirrhosis. Pulmonary parameters associated with death included Pao(2)/Fio(2) and oxygenation index ((mean airway pressurexFio(2)x100)/Pao(2)). In unadjusted analysis, the odds ratio (OR) of death for Pao(2)/Fio(2) was 1.57 (CI 1.12 to 3.04) per standard deviation decrease. However, in adjusted analysis, Pao(2)/Fio(2) was not a statistically significant predictor of death, with an OR of 1.29 (CI 0.82 to 2.02). In contrast, oxygenation index (OI) was a statistically significant predictor of death in both unadjusted analysis (OR 1.89 (CI 1.28 to 2.78)) and in adjusted analysis (OR 1.84 (CI 1.13 to 2.99)). CONCLUSIONS: In this cohort of patients with ALI/ARDS, OI was an independent predictor of mortality, whereas Pao(2)/Fio(2) was not. OI may be a superior predictor because it integrates both airway pressure and oxygenation into a single variable.

Low tidal volume ventilation is associated with reduced mortality in HIV-infected patients with acute lung injury.

BACKGROUND: Respiratory failure remains the leading indication for admission to the intensive care unit (ICU) and a leading cause of death for HIV-infected patients in spite of overall improvements in ICU mortality. It is unclear if these improvements are due to combination anti-retroviral therapy, low tidal volume ventilation for acute lung injury, or both. A study was undertaken to identify therapies and clinical factors associated with mortality in acute lung injury among HIV-infected patients with respiratory failure in the period 1996-2004. A secondary aim was to compare mortality before and after introduction of a low tidal volume ventilation protocol in 2000. METHODS: A retrospective cohort study was performed of 148 consecutive HIV-infected adults admitted to the ICU at San Francisco General Hospital with acute lung injury requiring mechanical ventilation. Demographic and clinical information including data on mechanical ventilation was abstracted from medical records and analysed by multivariate analysis using logistic regression. RESULTS: In-hospital mortality was similar before and after introduction of a low tidal volume ventilation protocol, although the study was not powered to exclude a clinically significant difference (risk difference -5.4%, 95% CI -21% to 11%, p = 0.51). Combination antiretroviral therapy was not clearly associated with mortality, except in patients with Pneumocystis pneumonia. Among all those with acute lung injury, lower tidal volume was associated with decreased mortality (adjusted odds ratio 0.76 per 1 ml/kg decrease, 95% CI 0.58 to 0.99, p = 0.043), after controlling for Pneumocystis pneumonia, serum albumin, illness severity, gas exchange impairment and plateau pressure. CONCLUSIONS: Lower tidal volume ventilation is independently associated with reduced mortality in HIV-infected patients with acute lung injury and respiratory failure.

Exacerbation of acute pulmonary edema during assisted mechanical ventilation using a low-tidal volume, lung-protective ventilator strategy.

STUDY OBJECTIVES: To assess the magnitude of negative intrathoracic pressure development in a patient whose pulmonary edema acutely worsened immediately following the institution of a low-tidal volume (VT) strategy. DESIGN: Mechanical lung modeling of patient-ventilator interactions based on data from a case report. SETTING: Medical ICU and laboratory. PATIENT: A patient with suspected ARDS and frank pulmonary edema. INTERVENTIONS: The patient's pulmonary mechanics and spontaneous breathing pattern were measured. Samples of arterial blood and pulmonary edema fluid were obtained. MEASUREMENTS: A standard work-of-breathing lung model was used to mimic the ventilator settings, pulmonary mechanics, and spontaneous breathing pattern observed when pulmonary edema worsened. Comparison of the pulmonary edema fluid-to-plasma total protein concentration ratio was made. RESULTS: The patient's spontaneous VT demand was greater than preset. The lung model revealed simulated intrathoracic pressure changes consistent with levels believed necessary to produce pulmonary edema during obstructed breathing. A high degree of imposed circuit-resistive work was found. The pulmonary edema fluid-to-plasma total protein concentration ratio was 0.47, which suggested a hydrostatic mechanism. CONCLUSION: Ventilator adjustments that greatly increase negative intrathoracic pressure during the acute phase of ARDS may worsen pulmonary edema by increasing the transvascular pressure gradient. Therefore, whenever sedation cannot adequately suppress spontaneous breathing (and muscle relaxants are contraindicated), a low-VT strategy should be modified by using a pressure-regulated mode of ventilation, so that imposed circuit-resistive work does not contribute to the deterioration of the patient's hemodynamic and respiratory status.

Implementation of a low tidal volume ventilation protocol for patients with acute lung injury or acute respiratory distress syndrome.

The ARDS (acute respiratory distress syndrome) Network study found 22% lower mortality in acute lung injury and ARDS patients ventilated with low tidal volumes (V(T)) than in those ventilated with traditional V(T) ventilation. Several points should be considered when using the low V(T) protocol for clinical practice. Prior to implementation, hemodynamic and acid-base status, minute ventilation, and adequacy of sedation should be assessed to minimize the potential for intolerance. The volume-preset, assist-control mode is recommended for better control of V(T), and the respiratory rate should be increased as V(T) is reduced, so as to maintain minute ventilation and prevent acute hypercapnia. When unavoidable, hypercapnia should be induced slowly. Ventilator inspiratory flow (V(I)) and trigger sensitivity settings should be optimized to limit the increase in work of breathing and dyspnea. When dyspnea results in double-triggered breaths, V(T) can be titrated to 7-8 mL/kg, provided end-inspiratory plateau pressure is < or = 30 cm H(2)O. In severe acidosis (pH < 7.15) V(T) also can be increased. However, every effort should be made to maintain plateau pressure and V(T) goals by buffering severe acidosis and treating patient-ventilator asynchrony with sedation. Evaluation for weaning should occur when adequate oxygenation can be maintained on 40% oxygen and a positive end-expiratory pressure of 8 cm H(2)O. Pressure support levels between 5 and 20 cm H(2)O (above 5 cm H(2)O positive end-expiratory pressure) are used for weaning and titrated to keep the respiratory rate < 35 breaths/min. Pressure support levels should be weaned aggressively, as long as the protocol's weaning tolerance criteria can be maintained.

The effects of pressure control versus volume control assisted ventilation on patient work of breathing in acute lung injury and acute respiratory distress syndrome.

BACKGROUND: Patient work of breathing (WOB) during assisted ventilation is reduced when inspiratory flow (V(I)) from the ventilator exceeds patient flow demand. Patients in acute respiratory failure often have unstable breathing patterns and their requirements for V(I) may change from breath to breath. Volume control ventilation (VCV) traditionally incorporates a pre-set ventilator V(I) that remains constant even under conditions of changing patient flow demand. In contrast, pressure control ventilation (PCV) incorporates a variable decelerating flow wave form with a high ventilator V(I) as inspiration commences. We compared the effects of flow patterns on assisted WOB during VCV and PCV. METHODS: WOB was measured with a BICORE CP-100 monitor (incorporating a Campbell Diagram) in a prospective, randomized cross-over study of 18 mechanically ventilated adult patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Tidal volume, inspiratory time, and mean ventilator V(I) were constant in each mode. RESULTS: At comparable levels of respiratory drive and minute ventilation, patient WOB was significantly lower with PCV than with VCV (0.59 +/- 0.42 J/L vs 0.70 +/- 0.58 J/L, respectively, p < 0.05). Ventilator peak V(I) was significantly higher with PCV than with VCV (103.2 +/- 22.8 L/min vs 43.8 L/min, respectively, p < 0.01). CONCLUSIONS: In the setting of ALI and ARDS, PCV significantly reduced patient WOB relative to VCV. The decrease in patient WOB was attributed to the higher ventilator peak V(I) of PCV.

Lung collapse during low tidal volume ventilation in acute respiratory distress syndrome.

BACKGROUND: Current ventilator management for acute respiratory distress syndrome (ARDS) incorporates low tidal volume (V(T)) ventilation in order to limit ventilator-induced lung injury. Low V(T) ventilation in supine patients, without the use of intermittent hyperinflations, may cause small airway closure, progressive atelectasis, and secretion retention. Use of high positive end-expiratory pressure (PEEP) levels with low V(T) ventilation may not counter this effect, because regional differences in intra-abdominal hydrostatic pressure may diminish the volume-stabilizing effects of PEEP. CASE SUMMARY: A 35-year-old man with abdominal compartment syndrome (intra-abdominal pressure > 48 cm H2O developed ARDS and was treated with V(T) of 4.5 mL/kg and PEEP of 20 cm H2O. Despite aggressive fluid therapy, appropriate airway humidification and tracheal suctioning, the patient developed complete bronchial obstruction, involving the entire right lung and left upper lobe. After bronchoscopy the patient was placed on a higher V(T) (7.0 mL/kg). Intermittent PEEP was instituted at 30 cm H2O for 2 breaths every 3 minutes. This intermittently raised the end-inspiratory plateau pressure from 38 cm H2O to 50 cm H2O. With the same airway humidity and tracheal suctioning practices bronchial obstruction did not reoccur. CONCLUSION: Low V(T) ventilation in ARDS may increase the risk of small airway closure and retained secretions. This adverse effect highlights the importance of pulmonary hygiene measures in ARDS during lung-protective ventilation.

Measuring intra-esophageal pressure to assess transmural pulmonary arterial occlusion pressure in patients with acute lung injury: a case series and review.

BACKGROUND: Positive end-expiratory pressure (PEEP) may interfere with accurate assessment of cardiac function. PEEP may decrease left ventricular volume by lowering the transmural gradient between ventricular and pleural surface pressure (P(PL)) around the heart while raising the absolute pulmonary arterial occlusion pressure (PAOP). Clinical formulas used to predict the transmural PAOP (PAOP(TM)) require subtracting 25-50% of the PEEP level from the PAOP. However, both PAOP and P(PL) are influenced by transmitted PEEP and transmitted intra-abdominal pressure (IAP). We compared PAOP(TM) calculated by measuring intra-esophageal pressure (P(ES)) with PAOP(TM) estimated by clinical formulas. METHODS: Twenty-two P(ES) measurements were made with a bedside pulmonary mechanics monitor (BICORE CP-100) on 11 patients with acute lung injury who had an elevated PAOP (mean +/- standard deviation) of 21.1 +/- 6.2 mm Hg and PEEP of 13.0 +/- 3.8 mm Hg. Paired comparisons were made with the Wilcoxon signed-rank test and multiple comparisons were made using one-way analysis of variance (ANOVA) and the Student-Newman-Keuls test. Pearson product-moment correlation coefficients were calculated. A MEDLINE literature search was done to survey the reported range of PEEP transmitted to P(PL). RESULTS: P(ES) (14.6 +/- 5.0 mm Hg) exceeded PEEP; 9 of 11 patients had clinical evidence of increased IAP. PAOP(TM) predicted by clinical formulas were 13.5-17.7 mm Hg, whereas PAOP(TM) calculated by P(ES) was 6.2 +/- 3.6 mm Hg (p < 0.05). Linear regression revealed a moderate correlation between PAOP and PEEP (r = 0.49, p = 0.02). In contrast, there was a strong correlation between PAOP and P(ES) (r = 0.83, p < 0.0001). A review of data derived from the literature did not show a consistent pattern of PEEP transmission. CONCLUSION: PAOP(TM) calculated by P(ES) may reflect transmitted IAP to the pleural surface. Using P(ES) to calculate PAOP(TM) may provide a more accurate assessment of hemodynamic status than predicting PAOP(TM) using clinical formulas based solely on estimated PEEP transmission.

Tracheal-innominate artery fistula caused by the endotracheal tube tip: case report and investigation of a fatal complication of prolonged intubation.

CASE REPORT: A patient with extensive burns was intubated with an 8.0 mm internal diameter endotracheal tube (ETT) equipped with a subglottic suction port (Mallinckrodt HiLo Evac). The ETT was secured to a left upper molar with wire sutures throughout the hospitalization course to ensure airway stability. On the 40th day of intubation, the patient exsanguinated and died from a tracheo-innominate artery fistula. Postmortem examination revealed a 1 cm lesion of the left anterior tracheal wall at the position of the ETT tip. The prolonged stationary position of the ETT was considered the primary factor responsible for the fistula. Yet tracheo-innominate artery fistula normally is associated with high cuff pressures rather than with the tube tip. The special ETT construction required for the subglottic suction feature was suspected to have increased tube rigidity and may have played a contributory role. METHODS: The rigidity of the Mallinckrodt HiLo Evac was measured with a mechanical model and compared to 5 other commercially-available ETTs. Rigidity was expressed as the force generated by the ETT tip when the tube curvature was altered by 5 cm and 10 cm of flexion from its resting position. RESULTS: The mean force exerted by the Mallinckrodt HiLo Evac was 10.1 +/- 2.8 g at 5 cm of flexion and 17.7 +/- 5.1 g at 10 cm of flexion. This was significantly greater than all other ETT brands tested (by one-way analysis of variance and Student-Newman-Kuels test, p < 0.05). CONCLUSION: This case of fatal tracheo-innominate artery fistula formation associated with an ETT tip was unusual because of the extended duration of endotracheal intubation and the complexity of the patient's airway management problems. Our data suggest that the higher rigidity of the HiLo Evac ETT may have contributed to fistula development at the tube tip. However, we do not believe that the higher rigidity of the HiLo Evac ETT necessarily poses any greater risk than other ETTs under normal circumstances, in which the tube tip is not fixed in a stationary position for an extended period.

Improved flow and pressure capabilities of the Datex-Ohmeda SmartVent anesthesia ventilator.

STUDY OBJECTIVE: To compare the flow and pressure capabilities of the Datex-Ohmeda SmartVent (Ohmeda 7900, Datex-Ohmeda, Madison, WI) to previous Ohmeda (7810 and 7000, Datex-Ohmeda, Madison, WI) anesthesia ventilators. To determine airway pressure and minute ventilation thresholds for intraoperative use of a critical care ventilator. DESIGN: Three anesthesia ventilators and one critical care ventilator (Siemens Servo 900C, Siemens, Solna, Sweden) were studied in a lung model. Retrospective medical record review. SETTING: Research Laboratory and Critical Care Unit of a Level I Trauma Center. PATIENTS: 145 mechanically ventilated patients treated for acute respiratory failure who underwent 200 surgical procedures. INTERVENTIONS: The effect of increasing pressure on mean inspiratory flow was determined by cycling each ventilator through increasing restrictors. Maximum minute ventilation was measured at low compliance (10-30 mL/cm H2O), positive end-expiratory pressure (PEEP) (0-20 cm H2O), and increased airway resistance (approximately 19 and approximately 36 cm H2O/L/sec) in a mechanical lung model. MEASUREMENTS AND MAIN RESULTS: Flow, volume, and pressure were measured with a pulmonary mechanics monitor (BICORE CP-100, Thermo Respiratory Group, Yorba Linda, CA). Preoperative peak airway pressure and minute ventilation (VE) were extracted from the medical record. Mean inspiratory flow declined with increasing pressure in all anesthesia ventilators. The SmartVent and the 7810 produced greater mean inspiratory flow than did the 7000 ventilator. As compliance progressively decreased, the Siemens, the SmartVent, and the 7810 ventilators maintained VE compared to the 7000 ventilator. The Siemens and the SmartVent maintained VE with PEEP, compared to the 7810 and 7000 ventilators. During increased airway resistance, maximal VE was lower for all ventilators. The SmartVent met the ventilation requirements in 90% of the patients compared to 67% of patients with the 7000 ventilator. CONCLUSION: The improved pressure and flow capabilities of the SmartVent increase the threshold for using a critical care ventilator intraoperatively to a peak airway pressure > 65 cm H2O and/or VE > 18 L/min.

Measuring dead-space in acute lung injury.

Several recent studies have advanced our understanding of dead-space ventilation in patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS). They have demonstrated the utility of measuring physiologic dead-space-to-tidal volume ratio (VD/VT) and related variables in assessing outcomes as well as therapeutic interventions. These studies have included the evaluation of mortality risk, pulmonary perfusion, as well as the effectiveness of drug therapy, prone positioning, positive end-expiratory pressure (PEEP) titration, and inspiratory pattern in improving gas exchange. In patients with ALI/ARDS managed with lung-protective ventilation a significant relationship between elevated VD/VT and increased mortality continues to be reported in both early and intermediate phases of ALI/ARDS. Some clinical evidence now supports the suggestion that elevated VD/VT in part reflects the severity of pulmonary vascular endothelial damage. Monitoring VD/VT also appears useful in assessing alveolar recruitment when titrating PEEP and may be a particularly expedient method for assessing the effectiveness of prone positioning. It also has revealed how subtle manipulations of inspiratory time and pattern can improve CO(2) excretion. Much of this has been accomplished using volumetric capnography. This allows for more sophisticated measurements of pulmonary gas exchange function including: alveolar VD/VT, the volume of CO(2) excretion and the slope of the alveolar plateau which reflects ventilation: perfusion heterogeneity. Many of these measurements now can be made non-invasively which should only increase the research and clinical utility of volumetric capnography in studying and managing patients with ALI/ARDS.

The treatment of acidosis in acute lung injury with tris-hydroxymethyl aminomethane (THAM).

Mechanical hyperventilation of acidemic patients with acute lung injury (ALI) requires the use of high volumes and pressures that may worsen lung injury. However, permissive hypercapnia in the presence of shock, metabolic acidosis, and multi-organ system dysfunction may compromise normal cellular function. Tris-hydroxymethyl aminomethane (THAM) may be an effective method to control acidosis in this circumstance. Protonated THAM is excreted by the kidneys, so that carbon dioxide production is not raised. In an uncontrolled study, we administered THAM to 10 patients with acidosis (mean pH = 7.14) and ALI (mean lung injury score = 3.28) in whom adequate control of arterial pH could not be maintained during either eucapnic ventilation or permissive hypercapnia ventilation. THAM was given at a mean dose of 0.55 mmol/kg/h. Administration of THAM was associated with significant improvements in arterial pH and base deficit, and a decrease in arterial carbon dioxide tension that could not be fully accounted for by ventilation. Although further studies are needed to confirm these observations, THAM appears to be an effective alternative to sodium bicarbonate for treating acidosis during ALI.