Reliability of transpulmonary pressure-time curve profile to identify tidal recruitment/hyperinflation in experimental unilateral pleural effusion.

The stress index (SI) is a parameter that characterizes the shape of the airway pressure-time profile (P/t). It indicates the slope progression of the curve, reflecting both lung and chest wall properties. The presence of pleural effusion alters the mechanical properties of the respiratory system decreasing transpulmonary pressure (Ptp). We investigated whether the SI computed using Ptp tracing would provide reliable insight into tidal recruitment/overdistention during the tidal cycle in the presence of unilateral effusion. Unilateral pleural effusion was simulated in anesthetized, mechanically ventilated pigs. Respiratory system mechanics and thoracic computed tomography (CT) were studied to assess P/t curve shape and changes in global lung aeration. SI derived from airway pressure (Paw) was compared with that calculated by Ptp under the same conditions. These results were themselves compared with quantitative CT analysis as a gold standard for tidal recruitment/hyperinflation. Despite marked changes in tidal recruitment, mean values of SI computed either from Paw or Ptp were remarkably insensitive to variations of PEEP or condition. After the instillation of effusion, SI indicates a preponderant over-distension effect, not detected by CT. After the increment in PEEP level, the extent of CT-determined tidal recruitment suggest a huge recruitment effect of PEEP as reflected by lung compliance. Both SI in this case were unaffected. We showed that the ability of SI to predict tidal recruitment and overdistension was significantly reduced in a model of altered chest wall-lung relationship, even if the parameter was computed from the Ptp curve profile.

Mechanical power at a glance: a simple surrogate for volume-controlled ventilation.

BACKGROUND: Mechanical power is a summary variable including all the components which can possibly cause VILI (pressures, volume, flow, respiratory rate). Since the complexity of its mathematical computation is one of the major factors that delay its clinical use, we propose here a simple and easy to remember equation to estimate mechanical power under volume-controlled ventilation: [Formula: see text] where the mechanical power is expressed in Joules/minute, the minute ventilation (VE) in liters/minute, the inspiratory flow (F) in liters/minute, and peak pressure and positive end-expiratory pressure (PEEP) in centimeter of water. All the components of this equation are continuously displayed by any ventilator under volume-controlled ventilation without the need for clinician intervention. To test the accuracy of this new equation, we compared it with the reference formula of mechanical power that we proposed for volume-controlled ventilation in the past. The comparisons were made in a cohort of mechanically ventilated pigs (485 observations) and in a cohort of ICU patients (265 observations). RESULTS: Both in pigs and in ICU patients, the correlation between our equation and the reference one was close to the identity. Indeed, the R2 ranged from 0.97 to 0.99 and the Bland-Altman showed small biases (ranging from + 0.35 to - 0.53 J/min) and proportional errors (ranging from + 0.02 to - 0.05). CONCLUSIONS: Our new equation of mechanical power for volume-controlled ventilation represents a simple and accurate alternative to the more complex ones available to date. This equation does not need any clinical intervention on the ventilator (such as an inspiratory hold) and could be easily implemented in the software of any ventilator in volume-controlled mode. This would allow the clinician to have an estimation of mechanical power at a simple glance and thus increase the clinical consciousness of this variable which is still far from being used at the bedside. Our equation carries the same limitations of all other formulas of mechanical power, the most important of which, as far as it concerns VILI prevention, are the lack of normalization and its application to the whole respiratory system (including the chest wall) and not only to the lung parenchyma.

Comparative effects of cyclophosphamide, isophosphamide, 4-methylcyclophosphamide, and phosphoramide mustard on murine hematopoietic and immunocompetent cells.

The effects of equimolal doses of cyclophosphamide (CY), isophosphamide (IP), 4-methylcyclophosphamide (4-MCY), and phosphoramide mustard (PM) on murine hematopoietic spleen colonies and adoptively transferred antibody-forming cells in vivo were compared. Equimolal doses of the drugs produced significantly different effects. All the drugs exerted an increasing effect against the ability of adoptively transferred immunocompetent cells to produce a significant anti-sheep red blood cell titer as the length of time between cell transfer and drug administration was increased. The maximum effect was seen when a drug was given 48--72 hours after antigen and spleen cell transfer. CY and IP produced significantly greater immunosuppressive effects than did the other drugs at all times after cell transfer and at all doses administered. PM had the least immunosuppressive effect at each dose evaluated. Against hematopoietic spleen colonies, the cytotoxic effects of 4-MCY and PM were similar and, at most doses studied, significantly greater than the effect of either CY or IP. Inasmuch as PM is an active metabolite of CY, it appeared either that one of the prior metabolites of CY was responsible for this marked immunosuppressive effect or that due to differences in polarity, PM was differentially distributed within the two cell systems as compared to CY. The differences in hematopoietic effects among all drugs were much less than those seen against immunocompetent cells and were not dependent on time of drug administration.

Experts' opinion on management of hemodynamics in ARDS patients: focus on the effects of mechanical ventilation.

RATIONALE: Acute respiratory distress syndrome (ARDS) is frequently associated with hemodynamic instability which appears as the main factor associated with mortality. Shock is driven by pulmonary hypertension, deleterious effects of mechanical ventilation (MV) on right ventricular (RV) function, and associated-sepsis. Hemodynamic effects of ventilation are due to changes in pleural pressure (Ppl) and changes in transpulmonary pressure (TP). TP affects RV afterload, whereas changes in Ppl affect venous return. Tidal forces and positive end-expiratory pressure (PEEP) increase pulmonary vascular resistance (PVR) in direct proportion to their effects on mean airway pressure (mPaw). The acutely injured lung has a reduced capacity to accommodate flowing blood and increases of blood flow accentuate fluid filtration. The dynamics of vascular pressure may contribute to ventilator-induced injury (VILI). In order to optimize perfusion, improve gas exchange, and minimize VILI risk, monitoring hemodynamics is important. RESULTS: During passive ventilation pulse pressure variations are a predictor of fluid responsiveness when conditions to ensure its validity are observed, but may also reflect afterload effects of MV. Central venous pressure can be helpful to monitor the response of RV function to treatment. Echocardiography is suitable to visualize the RV and to detect acute cor pulmonale (ACP), which occurs in 20-25 % of cases. Inserting a pulmonary artery catheter may be useful to measure/calculate pulmonary artery pressure, pulmonary and systemic vascular resistance, and cardiac output. These last two indexes may be misleading, however, in cases of West zones 2 or 1 and tricuspid regurgitation associated with RV dilatation. Transpulmonary thermodilution may be useful to evaluate extravascular lung water and the pulmonary vascular permeability index. To ensure adequate intravascular volume is the first goal of hemodynamic support in patients with shock. The benefit and risk balance of fluid expansion has to be carefully evaluated since it may improve systemic perfusion but also may decrease ventilator-free days, increase pulmonary edema, and promote RV failure. ACP can be prevented or treated by applying RV protective MV (low driving pressure, limited hypercapnia, PEEP adapted to lung recruitability) and by prone positioning. In cases of shock that do not respond to intravascular fluid administration, norepinephrine infusion and vasodilators inhalation may improve RV function. Extracorporeal membrane oxygenation (ECMO) has the potential to be the cause of, as well as a remedy for, hemodynamic problems. Continuous thermodilution-based and pulse contour analysis-based cardiac output monitoring are not recommended in patients treated with ECMO, since the results are frequently inaccurate. Extracorporeal CO2 removal, which could have the capability to reduce hypercapnia/acidosis-induced ACP, cannot currently be recommended because of the lack of sufficient data.

Mathematical models for pressure controlled ventilation of oleic acid-injured pigs.

One-compartment, mathematical models for pressure controlled ventilation, incorporating volume dependent compliances, linear and nonlinear resistances, are constructed and compared with data obtained from healthy and (oleic acid) lung-injured pigs. Experimental data are used to find parameters in the mathematical models and were collected in two forms. Firstly, the P(e)-V curves for healthy and lung injured pigs were constructed; these data are used to compute compliance functions for each animal. Secondly, dynamic data from pressure controlled ventilation for a variety of applied pressures are used to estimate resistance parameters in the models. The models were then compared against the collected dynamic data. The best mathematical models are ones with compliance functions of the form C(V) = a + bV where a and b are constants obtained from the P(e)-V curves and the resistive pressures during inspiration change from a linear relation P(r) = RQ to a nonlinear relation P(r) = RQ(epsilon) where Q is the flow into the one-compartment lung and epsilon is a positive number. The form of the resistance terms in the mathematical models indicate the possible presence of gas-liquid foams in the experimental data.

Improved oxygenation after muscle relaxation in adult respiratory distress syndrome.

Arterial blood oxygenation improved repeatedly after sedation and paralysis in a 27-year-old woman requiring mechanical ventilation for the adult respiratory distress syndrome. Oxygen consumption and cardiac output decreased proportionately after paralysis so that the partial pressure of oxygen in mixed venous blood remained unchanged. Paralysis eliminated inspiratory distortion of the airway pressure waveform and prevented forceful use of expiratory musculature. A flow-related reduction of venous admixture or recruitment of lung volume may best explain the beneficial effect of muscle relaxation on arterial saturation.

Magnesium toxicity as a cause of hypotension and hypoventilation. Occurrence in patients with normal renal function.

Symptomatic hypermagnesemia usually requires both increased intake of the ion and abnormal renal function; however, we treated two patients with iatrogenic hypermagnesemia (10.4 and 13.2 mEg/L) who had normal renal function. One received ureteral irrigation with hemiacidrin (Renacidin) to dissolve a stone, and the other was treated for ingestion of an unknown toxin with large doses of magnesium sulfate. Therapy included ventilatory support, intravenous calcium, and fluids. Dialysis was not required, and recovery was complete.

Transbronchial needle aspiration of a bronchial carcinoid tumor.

We biopsied a suspected bronchial carcinoid tumor with a transbronchial aspiration needle and obtained cytologic diagnosis without significant hemorrhage. This technique may prove valuable in sampling highly vascular endobronchial neoplasms.

Inverse ratio ventilation in ARDS. Rationale and implementation.

Conventional ventilatory support of patients with the adult respiratory distress syndrome (ARDS) consists of volume-cycled ventilation with applied positive end-expiratory pressure (PEEP). Unfortunately, recent evidence suggests that this strategy, as currently implemented, may perpetuate lung damage by overinflating and injuring distensible alveolar tissues. An alternative strategy--termed inverse ratio ventilation (IRV)--extends the inspiratory time, and, in concept, maintains or improves gas exchange at lower levels of PEEP and peak distending pressures. There are two methods to administer IRV: (1) volume-cycled ventilation with an end-inspiratory pause, or with a slow or decelerating inspiratory flow rate; or (2) pressure-controlled ventilation applied with a long inspiratory time. There are several real or theoretical problems common to both forms of IRV: excessive gas-trapping; adverse hemodynamic effects; and the need for sedation in most patients. Although there are many anecdotal reports of IRV, there are no controlled studies that compare outcome in ARDS patients treated with IRV as opposed to conventional ventilation. Nonetheless, clinicians are using IRV with increasing frequency. In the absence of well-designed clinical trials, we present interim guidelines for a ventilatory strategy in patients with ARDS based on the literature and our own clinical experience.

Validation of a technique to assess maximal inspiratory pressure in poorly cooperative patients.

The maximal pressure that can be generated during an inspiratory effort against an occluded airway serves as an index of respiratory muscle strength. We devised a method that permits accurate measurement of MIP, with near maximal values, and does not require patient cooperation. Twenty-two critically ill intubated patients performed MIP maneuvers before and after coaching. For the initial 11 patients, MIP was measured after the airway was occluded in 20 s with a one-way valve that permitted only exhalation. In the latter 11 patients, DS (approximately 1/3 VT) was added in an effort to increase respiratory drive before the noncoached MIP maneuver. We found no significant difference between coached and noncoached MIP maneuvers when P0.1 during the first 100 ms of inspiratory efforts prior to the noncoached MIP maneuver was greater than 2 cm H2O. Thus, MIP can be reliably measured in critically ill patients with or without coaching.

The effect of atropine inhalation in "irreversible" chronic bronchitis.

Fifteen patients with chronic bronchitis and airflow obstruction which was not improved by inhalation of isoproterenol (increase in forced expiratory volume in one second [FEV1] less than 15 percent) received an aerosol of atropine sulfate (0.05 mg/kg of body weight), in order to determine their response to an anticholinergic bronchodilator drug. The improvement over initial values for FEV1 at 15 minutes following inhalation of isoproterenol and at 90 minutres following inhalation of atropine averaged 5.9 percent and 19.2 percent, respectively (P less than 0.01). Eleven of 15 patients demonstrated a 15 percent or greater increase in FEV1 following inhalation of atropine, and six subjects demonstrated more than 25 percent improvement. The maximum effect of atropine was observed at or later than 90 minutes following inhalation in nine of 11 patients who were responsive to atropine. Minimal systemic toxic effects resulted from inhalation of atropine, although dryness of the mouth was frequent. In patients with chronic bronchitis, airflow obstruction resistant to isoproterenol may respond to inhalation of an aerosol of atropine sulfate.

Bedside estimation of the inspiratory work of breathing during mechanical ventilation.

The work of chest inflation, WI, is a primary determinant of the need for ventilatory support and an integrative index of elastic and resistive impedance. Although the mechanical work performed by a ventilator in moving gas into the passive chest (WI = integral of PV dt) can be determined by measuring the area enclosed by a display of airway pressure (P) against delivered volume (V), the instrumentation required is not routinely available at the bedside. Under conditions of constant flow, however, inspiratory time represents an analog of delivered volume, and airway pressure can be recorded easily by equipment normally employed to monitor pulmonary vascular pressures. We reasoned that the area beneath the airway pressure vs time tracing should accurately reflect WI for unassisted breaths delivered by the ventilator at constant flow. We computed estimates of WI from simultaneous pressure-volume (PV) and pressure-time (PT) plots during square-wave inflation in 20 acutely ill patients. Ventilator settings were varied over the usual clinical range for tidal volume (10 to 15 ml/kg) and inspiratory flow (40 to 80 L/min). PV and PT estimates agreed closely; across the four setting combinations tested, the difference between PV and PT estimates averaged 2.4 +/- 5.6 percent (means +/- SD, r = 0.99). Furthermore, the reproducible geometric configuration of the curves generated allowed accurate estimation of WI from routine beside observations of tidal volume and peak dynamic and static inflation pressures, without the need for specialized equipment or area measurement. Such simplified estimates could serve in clinical practice to gauge the ventilatory workload and to monitor changes in respiratory impedance.

Effect of tracheal gas insufflation on demand valve triggering and total work during continuous positive airway pressure ventilation.

Tracheal gas insufflation (TGI) improves CO2 clearance and may reduce work of breathing by lowering the required minute ventilation (VE). However, TGI might also impair the ability to trigger the ventilator, because to lower external circuit pressures, inspiratory effort must outstrip catheter flow rate (Vc) and overcome the dynamic hyperinflation caused by TGI. We studied these effects using a two-chamber lung model of the respiratory muscles (RM) and lungs (L). The RM-chamber was ventilated using a sinusoidal flow pattern with a tidal volume (VT) of 0.5 L at various peak inspiratory flow rates (Vpk) to simulate differences in effort intensity. The L-chamber was connected to a 60-L/min continuous flow circuit with a 10 cm H2O positive end-expiratory pressure valve and to 3 different ventilatory demand valve circuits, each set at continuous positive airway pressure (CPAP) of 10 cm H2O. We used continuous TGI at 0, 2.5, 5, 10, and 15 L/min. The work of triggering (W-trig) increased with increasing Vc and decreased with increasing Vpk. The L-ventilator failed to trigger when Vc was 15 L/min and Vpk was 20 L/min. At a fixed VE, the effect of TGI on total mechanical inspiratory work (W-tot) was relatively small and varied among the different CPAP systems used. We conclude that weak patients may fail to open the demand valve of the CPAP system during TGI at high catheter flow rates. The net effect of TGI on the effort made by ventilated patients would depend not only on the interactions between TGI and the ventilator, but also on the efficiency of TGI in decreasing dead-space and lowering the VE requirement.

Atropine and terbutaline aerosols in chronic bronchitis: efficacy and sites of action.

To examine the additive properties and the sites of action of inhaled atropine sulfate (0.05 mg/kg of body weight) and terbutaline sulfate (0.005 mg/kg) in patients with chronic airflow obstruction, we tested these aerosols separately and together in a double-blind random sequence. Twelve patients with chronic bronchitis and perennial obstruction of airflow were studied by measuring three indices of efficacy (specific airway conductance [Gaw/VL], the forced expiratory volume in one second [FEV1] and the forced vital capacity [FVC]) and three indices of the site of action within the airway (delta [(Gaw/VL)/FEV1], the difference between the change in forced expiratory flow at 75 percent of vital capacity and the change in forced expiratory flow at 25 percent of vital capacity, and the change in density dependence of maximal airflow at 50 percent of vital capacity). Both atropine and the combination of atropine and terbutaline improved all indices of efficacy significantly more than did terbutaline. With individual exceptions, the addition of terbutaline to atropine improved Gaw/VL but not forced airflow. All measures of site of action suggested an advantage for atropine in relatively proximal airways. These results indicate that combined therapy with beta-adrenergic and anticholinergic bronchodilator drugs is marginally more effective than therapy with atropine alone in these patients and suggest that anticholinergic aerosols dilate larger airways more effectively than the beta-agonists.

The inspiratory work of breathing during assisted mechanical ventilation.

We quantified the mechanical work of breathing in six normal subjects during assisted mechanical ventilation. Using two volume-cycled ventilators of different design, we investigated the influence of minute ventilation (VE) and machine settings of trigger sensitivity and flow during CO2-driven hyperventilation to moderate and high levels (12-24 L/min). Work estimates were derived from plots of esophageal and airway pressure against inflation volume. Peak flow and trigger sensitivity were important determinants of the energy expended, and for each combination of machine settings the work done by the subject per liter of ventilation increased with VE. During assisted ventilation the subject expended energy equivalent to 33-50 percent of the work of passive inflation, even under the most favorable conditions of VE, sensitivity and flow. Under the least favorable conditions of VE, sensitivity and flow, the subject's inspiratory work of breathing substantially exceeded the energy needed by the ventilator to inflate the passive thorax. These observations imply that exertion of the respiratory muscles continues throughout inflation during assisted mechanical ventilation and call attention to the possibility that inappropriate selection of ventilatory mode or machine settings may contribute to respiratory muscle fatigue and dyspnea.

Volume-cycled decelerating flow. An alternative form of mechanical ventilation.

The linearly decelerating flow waveform for volume-cycled mechanical ventilation is an option on many modern ventilators. We have developed mathematical models for two available forms of volume-cycled decelerating-flow ventilation (VCDF). These equations use clinician-chosen ventilator settings as inputs (frequency, tidal volume, peak inspiratory flow or inspiratory time fraction, and end-inspiratory pause), and patient-determined inputs which describe the patient's ventilatory impedance (inspiratory [RI] and expiratory [RE] resistance and respiratory system compliance [C]. The equations predict key outcome variables: mean airway pressure; and peak, mean, and end-expiratory alveolar pressures. The mathematical expressions were validated in a mechanical lung analog. Values observed in the test lung were compared to values predicted by the mathematical models for a wide range of ventilator settings and impedance combinations (RI and RE, 5 to 40 cm H2O.s/L; C, 0.02 to 0.10 L/cm H2O). The correspondence between observed and predicted values was generally excellent across the broad range of inputs tested (r greater than or equal to 0.98). Outcome variables were quite sensitive to clinician-chosen inputs over certain critical ranges. Carefully applied, VCDF offers several theoretic advantages for the clinical setting; however, appropriate caution must be exercised to avoid the application of tissue-injuring pressure.

Effect of a nasogastric tube on esophageal pressure measurement in normal adults.

We studied the correspondence between fluctuations of esophageal pressure measured before and after placement of a nasogastric (NG) tube in six normal volunteers. Flow, airway pressure, and esophageal pressure data from at least 20 breaths were recorded in seven ventilatory conditions in two body postures: 0 degree (supine) and 60 degrees (upright). The conditions studied included normal quiet breathing, added resistance, reduced compliance, increased frequency, increased tidal volume, continuous positive airway pressure, and volume-cycled ventilation with positive pressure. During recording with the NG tube in place, the subject targeted the same tidal volume (VT), respiratory rate, and inspiratory time fraction (TI/TTOT) recorded before NG tube placement. A computer program selected for analysis only those recorded breaths with and without an NG tube that were "matched" within 5 percent for both VT and TI. We calculated average VT, TI, and esophageal pressure fluctuation (delta Pes) for the matched breaths from each subject during every condition. The delta Pes values with and without NG tube were not statistically different in any tested condition (p > 0.05). Our data indicate that the presence of an NG tube does not invalidate the accuracy of delta Pes measurements made using a well-positioned balloon catheter in the tested conditions.

Variability of arterial blood gas values in stable patients in the ICU.

To establish guidelines for the interpretation of changes in arterial blood gas (ABG) values, we studied 29 clinically stable ICU patients for spontaneous variability in PaO2, PaCO2 and pH. ABGs were sampled six times over a 50-minute period, during which all patients received a fixed FIO2 of 0.5 via endotracheal tube and underwent no therapeutic interventions. Each sample was analyzed in duplicate with careful attention to method of collection and measurement. The range separating the lowest and highest PaO2 varied from 1 to 45 mm Hg (16.2 +/- 10.9 mm Hg [mean +/- SD] ). For PaCO2 this range was from 1 to 8 mm Hg (3.0 +/- 1.9 mm Hg). Coefficient of variation for PaO2 and PaCO2 averaged 5.1 +/- 3.2 percent (mean +/- SD) and 3.0 +/- 1.5 percent respectively. pH varied within 0.03 +/- 0.02 units. Percentage change in PaO2 between sequential intrapatient samples averaged 5.3 +/- 2.8 percent (mean +/- SD) and 7.1 +/- 7.9 percent over ten- and 50-minute intervals, respectively. Various clinical features were analyzed by multiple regression analysis for their relation to PaO2 variation. Only leukocyte count and mean arterial oxygen content were statistically significant associations (p less than 0.05), but together explained less than 35 percent of the variation observed. Because considerable spontaneous variation occurs, even in stable patients, clinicians should base therapeutic decisions on trends in PaO2 values rather than on isolated changes interpreted without appropriate clinical correlation.

Round table conference on ventilatory failure, Brussels, Belgium, March 16-18, 1991.

It was possible to reach agreement on several important issues relating to VF. First, the phenomenon of CO2 retention may have both pathophysiologic and compensatory components. There is increased awareness of the nature, intensity, and significance of the cross-talk between the ventilatory control center and the pump itself, as expressed in breathing pattern and indices of ventilatory drive. We are learning to interpret that information more effectively to assess functional reserve. Second, knowledge concerning the relative importance of various muscle groups is still incomplete, and the impact of disease on muscle function, lung mechanics, and ventilatory control is not fully understood. Dynamic hyperinflation and sleep disturbances provide two clear examples of conditions whose wide-ranging influence on drive, workload, and muscle function was, until quite recently, under appreciated. Finally, there was a general consensus that our therapeutic approaches to VF should be modified to reflect improved understanding of the pathogenesis of CO2 retention and iatrogenic lung injury. In the acute setting, measures to limit alveolar distention, such as controlling airway pressure, revising blood gas targets, and/or using adjunctive methods for blood gas exchange may avoid barotraumatic edema and rupture. The potential for non-invasive ventilation to avert intubation, facilitate ventilator withdrawal, and help patients with chronic VF to achieve compensation without machine dependence is now being actively investigated. This two day conference proved a stimulating forum for interchange of ideas regarding the state of the field, and allowed many opportunities for scientific interaction, both during outside the formal program.(ABSTRACT TRUNCATED AT 250 WORDS)