David N. Hager

A protocol for high-frequency oscillatory ventilation in adults: Results from a roundtable discussion*

Objective:Ventilator settings typically used for high-frequency oscillatory ventilation (HFO) in adults provide acceptable gas exchange but may not take best advantage of its lung-protective aspects. We provide guidelines for HFO in adults with acute respiratory distress syndrome that should optimize the lung-protective characteristics of this ventilation mode. Design:Roundtable discussions, iterative revisions, and consensus. Setting:Five academic medical centers. Patients:Not applicable. Interventions:Participants addressed how to best maintain ventilation through combinations of oscillation pressure amplitude, frequency, and the use of an endotracheal tube cuff leak, and to maintain oxygenation through combinations of recruitment maneuvers, mean airway pressure, and oxygen concentration. The guiding principles were to provide lung protective ventilation by minimizing the size of tidal volumes, and balance the risks and benefits of lung recruitment and distension. Main Results:HFO may provide smaller tidal volumes and more complete lung recruitment than conventional modes. To optimize these features, we recommend use of the maximum pressure-oscillation amplitude coupled with the highest tolerated frequency, targeting a pH of only 7.25–7.35. This will yield a smaller tidal volume than typical HFO settings where frequency is limited to 6 Hz or less and pressure amplitude is submaximal. Lung recruitment can be achieved with the use of recruitment maneuvers, especially during the first several days of HFO. Recruitment may be augmented or sustained with generous mean airway pressures. These may either be chosen from a table of recommended mean airway pressure and oxygen concentration combinations, or individually titrated based on the oxygenation response of each patient. Conclusions:Modification of the goals and tactics of HFO use may better protect against ventilator-associated lung injury. Further clinical trials are needed to compare the effects on patient outcome of the best use of HFO compared to the most protective use of conventional modes in adult acute respiratory distress syndrome.

Tidal volume delivery during high-frequency oscillatory ventilation in adults with acute respiratory distress syndrome.

Objective:a) Characterize how ventilator and patient variables affect tidal volume during high-frequency oscillatory ventilation; and b) measure tidal volumes in adults with acute respiratory distress syndrome during high-frequency oscillatory ventilation. Design:Observational study. Setting:Research laboratory and medical intensive care unit. Patients:Test lung and patients with acute respiratory distress syndrome. Interventions:Using a previously validated hot wire anemometer placed in series with a Sensormedics 3100B high-frequency ventilator, an endotracheal tube, and a test lung, tidal volume was measured at different combinations of frequency (4, 6, 8, 10, and 12 Hz), pressure amplitude (50, 60, 70, 80, and 90 cm H2O), mean airway pressure (20, 30, and 40 cm H2O), test lung compliance (10, 30, and 50 mL/cm H2O), endotracheal tube internal diameter (6, 7, and 8 mm), bias flow (20, 30, and 40 L/min), and inspiratory/expiratory ratio (1:2 and 1:1). In patients, tidal volume was measured at baseline ventilator settings and at baseline frequency ±2 Hz and baseline pressure amplitude ±10 cm H2O. Measurements and Main Results:Measured tidal volumes were 23–225 mL during high-frequency oscillatory ventilation of the test lung. A 2-Hz increase in frequency and a 10-cm H2O increase in pressure amplitude caused a 21.3% ± 4.1% decrease and 21.4% ± 3.4% increase in tidal volume, respectively. Decreasing endotracheal tube internal diameter from 8 mm to 7 mm and from 7 mm to 6 mm caused a 15.3% ± 1.7% and 18.9% ± 2.1% reduction in tidal volume, respectively. Increasing bias flow from 20 L/min to 30 L/min increased tidal volume by 11.2% ± 3.9%. Further increases in bias flow, changes in compliance, and changes in mean airway pressure had little effect. Tidal volumes measured in acute respiratory distress syndrome patients were 44–210 mL. A 2-Hz increase in frequency was associated with a 23.1% ± 6.3% decrease in tidal volume. In contrast to the test lung data, a 10-cm H2O increase in pressure amplitude resulted in only a 5.6% ± 4.5% increase in tidal volume. Conclusions:Tidal volumes are not uniformly small during high-frequency oscillatory ventilation. The primary determinant of tidal volume in adults with acute respiratory distress syndrome during high-frequency oscillatory ventilation with the Sensormedics 3100B is frequency. Test lung findings suggest that endotracheal tube internal diameter is also an important determinant of tidal volume.

A targeted real-time early warning score (TREWScore) for septic shock

TREWScore, a targeted early warning score for septic shock, identifies patients who develop septic shock before the onset of sepsis-related organ failure. Evening the score against sepsis Sepsis is a major cause of death, which remains difficult to treat despite modern antibiotics. Early aggressive treatment of this disease improves patient mortality, but the tools currently available in the clinic do not predict who will develop sepsis and its late manifestation, septic shock, until the patients are already in advanced stages of the disease. Henry et al. used readily available data from patient monitors and medical records to develop TREWScore, a targeted real-time early warning score that predicts in advance which patients are at risk for septic shock. With a median lead time of over 24 hours, this scoring algorithm may allow clinicians enough time to intervene before the patients suffer the most damaging effects of sepsis. Sepsis is a leading cause of death in the United States, with mortality highest among patients who develop septic shock. Early aggressive treatment decreases morbidity and mortality. Although automated screening tools can detect patients currently experiencing severe sepsis and septic shock, none predict those at greatest risk of developing shock. We analyzed routinely available physiological and laboratory data from intensive care unit patients and developed “TREWScore,” a targeted real-time early warning score that predicts which patients will develop septic shock. TREWScore identified patients before the onset of septic shock with an area under the ROC (receiver operating characteristic) curve (AUC) of 0.83 [95% confidence interval (CI), 0.81 to 0.85]. At a specificity of 0.67, TREWScore achieved a sensitivity of 0.85 and identified patients a median of 28.2 [interquartile range (IQR), 10.6 to 94.2] hours before onset. Of those identified, two-thirds were identified before any sepsis-related organ dysfunction. In comparison, the Modified Early Warning Score, which has been used clinically for septic shock prediction, achieved a lower AUC of 0.73 (95% CI, 0.71 to 0.76). A routine screening protocol based on the presence of two of the systemic inflammatory response syndrome criteria, suspicion of infection, and either hypotension or hyperlactatemia achieved a lower sensitivity of 0.74 at a comparable specificity of 0.64. Continuous sampling of data from the electronic health records and calculation of TREWScore may allow clinicians to identify patients at risk for septic shock and provide earlier interventions that would prevent or mitigate the associated morbidity and mortality.

Feasibility of very high-frequency ventilation in adults with acute respiratory distress syndrome

Objective:To assess the feasibility of using respiratory frequencies up to 15 Hz during high-frequency oscillatory ventilation (HFO) of adults with acute respiratory distress syndrome (ARDS). Design:Observational study. Setting:Medical intensive care unit at a tertiary care university hospital. Patients:Thirty adult patients receiving HFO at the discretion of their physicians for management of severe ARDS. Interventions:Clinical management algorithm for HFO that minimized delivered tidal volumes by encouraging the use of the highest frequency that allowed acceptable clearance of carbon dioxide. This contrasts with the typical use of HFO in adults, in which frequencies generally do not exceed 6 Hz. Measurements and Main Results:Patients were 42 ± 15 yrs old, weighed 83 ± 25 kg, and had failed conventional lung-protective ventilation due to refractory hypoxia or respiratory acidosis and high plateau airway pressures. During HFO, 25 of 30 patients maintained acceptable gas exchange at frequencies >6 Hz; 12 reached maximal frequencies of ≥10 Hz. Among patients whose maximal frequencies exceeded 6 Hz, mean maximal frequency was 9.9 ± 2.1 Hz, at a mean oscillation pressure amplitude of 81 ± 11 cm H2O. At those settings, blood gases were pH 7.31 ± 0.06, Paco2 was 58 ± 21 mm Hg, and Pao2 was 82 ± 33 mm Hg. Survival to hospital discharge among this severely ill cohort was 37%. Conclusions:Most adults can maintain adequate gas exchange using HFO frequencies well above 5–6 Hz. Use of higher frequencies should minimize tidal volume and we speculate might thereby reduce ventilator-associated lung injury.

Reducing Deep Sedation and Delirium in Acute Lung Injury Patients: A Quality Improvement Project*

Objective:Deep sedation and delirium are common in the ICU. Mechanically ventilated patients with acute lung injury are at especially high risk for deep sedation, delirium, and associated long-term physical and neuropsychiatric impairments. We undertook an ICU-wide structured quality improvement project to decrease sedation and delirium. Design:Prospective quality improvement project in comparison with a retrospective acute lung injury control group. Setting:Sixteen-bed medical ICU in an academic teaching hospital with pre-existing use of goal-directed sedation with daily interruption of sedative infusions. Patients:Consecutive acute lung injury patients. Intervention:A “4Es” framework (engage, educate, execute, evaluate) was used as part of the quality improvement process. A new sedation protocol was created and implemented, which recommends a target Richmond Agitation Sedation Scale score of 0 (alert and calm) and requires failure of intermittent sedative dosing prior to starting continuous infusions. In addition, twice-daily delirium screening using the Confusion Assessment Method for the ICU was introduced into routine practice. Measurements and Main Results:Sedative use and delirium status in acute lung injury patients after implementation of the quality improvement project (n = 82) were compared with a historical control group (n = 120). During the quality improvement vs. control periods, use of narcotic and benzodiazepine infusions were substantially lower (median proportion of medical ICU days per patient: 33% vs. 74%, and 22% vs. 70%, respectively, both p < 0.001). Further, wakefulness increased (median Richmond Agitation Sedation Scale score per patient: −1.5 vs. −4.0, p < 0.001), and days awake and not delirious increased (median proportion of medical ICU days per patient: 19% vs. 0%, p < 0.001). Conclusion:Through a structured quality improvement process, use of sedative infusions can be substantially decreased and days awake without delirium significantly increased, even in severely ill, mechanically ventilated patients with acute lung injury.

Quantifying mechanical heterogeneity in canine acute lung injury : Impact of mean airway pressure

Background:The heterogeneous pattern of acute lung injury (ALI) predisposes patients to ventilator-associated lung injury. Currently, there is no simple technique that can reliably quantify lung heterogeneity during the dynamic conditions of mechanical ventilation. Such a technique may be of use in optimizing mechanical ventilatory parameters such as rate, tidal volume, or positive end-expiratory pressure. Methods:To determine the impact of heterogeneity on respiratory mechanics, the authors measured respiratory impedance (Zrs), expressed as respiratory resistance (Rrs) and elastance (Ers), in 11 anesthetized dogs from 0.078 to 8.9 Hz using broadband pressure and flow excitations under baseline conditions and after ALI produced by infusion of 0.08 ml/kg oleic acid into the right atrium. Data were obtained at mean airway pressures (&OV0440;ao) of 5, 10, 15, and 20 cm H2O. The Zrs spectra were fit by various models of the respiratory system incorporating different distributions of parallel viscoelastic tissue properties. Results:Under baseline conditions, both Rrs and Ers exhibited dependence on oscillation frequency, reflecting viscoelastic behavior. The Ers demonstrated significant dependence on &OV0440;ao. After ALI, both the level and frequency dependence of Rrs and Ers increased, as well as the apparent heterogeneity of tissue properties. Both Rrs and Ers as well as heterogeneity decreased with increasing &OV0440;ao, approaching baseline levels at the highest levels of &OV0440;ao. Conclusions:These data demonstrate that Zrs can provide specific information regarding the mechanical heterogeneity of injured lungs at different levels of &OV0440;ao. Moderate increases in &OV0440;ao seem to be beneficial in ALI by reducing heterogeneity and recruiting lung units. These noninvasive measurements of lung heterogeneity may ultimately allow for the development of better ventilation protocols that optimize regional lung mechanics in patients with ALI.

Four methods of measuring tidal volume during high-frequency oscillatory ventilation.

Objective:Assess the accuracy of four different methods of measuring tidal volume during simulated high-frequency oscillatory ventilation. Design:In vitro study. Setting:Research laboratory. Subjects:Three differential pressure pneumotachometers, a modified Pitot tube, an ultrasound flowmeter, and an adult hot wire anemometer. Interventions:Each device was placed in series with a Sensormedics 3100B high-frequency ventilator and an 8.0-mm endotracheal tube attached to a 48.9-L plethysmograph. Inspiratory/expiratory ratio was fixed at 1:1 and mean airway pressure at 10 cm H2O. Tidal volumes were calculated at each combination of frequency (f: 3, 4, 6, 8, 10, 12 Hz) and pressure amplitude (ΔP: 30, 60, 90 cm H2O) by digital integration of the sampled flow signals from each device and compared with those calculated from pressure changes within the plethysmograph. The protocol was repeated after incorporation of frequency-specific calibrations to the flow-measuring algorithm of each device. The hot wire anemometer was further evaluated at Fio2 of 1.0, 37°C, 80% humidity, mean airway pressure of 20 cm H2O, and an inspiratory/expiratory ratio of 1:2. Measurements and Main Results:Tidal volumes were 36–305 mL. Bland-Altman analysis demonstrated that each device exhibited systematic bias before frequency-specific adjustment. After frequency-specific adjustment of the flow-measuring algorithm, the two most accurate and precise devices were the Hans Rudolph pneumotachometer, which exhibited a mean error of 0.2% (95% confidence interval, −3.0% to 3.4%), and the hot wire anemometer, which had a mean error of −1.1% (95% confidence interval, −5.5% to 3.3%). The hot wire anemometer remained accurate at Fio2 1.0, 37°C, 80% humidity, mean airway pressure of 20 cm H2O, and an inspiratory/expiratory ratio of 1:2. Conclusions:Tidal volume can be measured during high-frequency oscillatory ventilation using a variety of techniques. Frequency-specific calibration improves the accuracy and precision of tidal volume measurements. Hot wire anemometry exhibits stable performance characteristics across the range of temperature, humidity, Fio2, and inspiratory/expiratory ratios encountered clinically, has a small deadspace, is unaffected by mean airway pressure, and is therefore suitable for clinical applications.

Recent Advances in the Management of the Acute Respiratory Distress Syndrome.

Advances in management of the acute respiratory distress syndrome (ARDS) include the use of volume and pressure-limited ventilation and a fluid conservative strategy. Despite the extensive study of positive end expiratory pressure, consensus regarding the best approach to its application is lacking. The use of neuromuscular blocking agents and prone positioning in the setting of refractory hypoxemia is supported by the outcomes of recent studies. Alternate modes of ventilation remain unproven. A focus on ARDS risk factor reduction and the development of tools predicting progression to ARDS have the potential to further reduce its incidence.

Total and Regional Lung Volume changes during High-Frequency Oscillatory Ventilation (HFOV) of the normal lung

The effect of high-frequency oscillatory ventilation (HFOV) settings on the distribution of lung volume (V(L)) with changes in mean airway pressure (Paw), frequency (f(R)) and tidal volume (V(T)) remains controversial. We used computer tomographic (CT) imaging to quantify the distribution of V(L) during HFOV compared to static continuous positive airway pressure (CPAP). In anesthetized, supine canines, CT imaging of the entire lung was performed during CPAP and HFOV at Paw of 5, 12.5 and 20 cm H(2)O, f(R)=5, 10, 15 Hz. We found small, statistically significant decreases compared with CPAP in total and regional V(L) during HFOV that were greatest at lower f(R) and Paw. Apex and base sub-volumes underwent changes comparable to the lung overall. Increases in f(R) were accompanied by increases in Pa(O)(2). These finding provide additional insight into the impact of HFOV settings on the distribution of V(L) and suggest that there is low risk of occult regional over-distention during HFOV in normal lungs.

In vitro performance comparison of the Sensormedics 3100A and B high-frequency oscillatory ventilators.

Objective: The Sensormedics 3100A and 3100B are widely used to provide high-frequency oscillatory ventilation in clinical practice. Infants and children <35 kg are typically oscillated with the 3100A and >35 kg with the 3100B. This study compares the effect of ventilator and patient parameters on delivered tidal volume during high-frequency oscillatory ventilation of a test lung with these devices. Design: Laboratory-based study. Subjects: Test lung and Sensormedics 3100A and 3100B high-frequency oscillators. Interventions: A previously validated hot-wire flowmeter (Florian) was placed in series with either a 3100A (n = 3) or 3100B (n = 3) ventilator and a Michigan test lung. Tidal volumes were measured over a range of mean airway pressure, inspiratory:expiratory ratio, frequency, pressure amplitude, and endotracheal tube internal diameter. Measurements and Main Results: The 3100A and 3100B delivered similar tidal volumes across a range of ventilator parameters for an inspiratory:expiratory ratio of 1:1, differing by <10%. However, at an inspiratory:expiratory ratio of 1:2, there was a statistically significant decrease in tidal volume for the 3100B compared with the 3100A at lower frequencies, which was partially mitigated by increasing pressure amplitude. The difference in the generated pressure and flow waveforms may account for the observed tidal volume differences between the high-frequency oscillatory ventilation models. Delivered tidal volume was highly dependent on endotracheal tube size. Conclusions: Multiple variables contribute to the delivered tidal volume during high-frequency oscillatory ventilation, including ventilator model selection and endotracheal tube size. It is possible that real-time, clinical monitoring of delivered tidal volume during high-frequency oscillatory ventilation would allow better titration and maximize performance of these ventilators in caring for critically ill patients.