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Ventilatory Failure, Ventilator Support, and Ventilator Weaning

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Abstract

The development of acute ventilatory failure represents an inability of the respiratory control system to maintain a level of respiratory motor output to cope with the metabolic demands of the body. The level of respiratory motor output is also the main determinant of the degree of respiratory distress experienced by such patients. As ventilatory failure progresses and patient distress increases, mechanical ventilation is instituted to help the respiratory muscles cope with the heightened workload. While a patient is connected to a ventilator, a physician's ability to align the rhythm of the machine with the rhythm of the patient's respiratory centers becomes the primary determinant of the level of rest accorded to the respiratory muscles. Problems of alignment are manifested as failure to trigger, double triggering, an inflationary gas‐flow that fails to match inspiratory demands, and an inflation phase that persists after a patient's respiratory centers have switched to expiration. With recovery from disorders that precipitated the initial bout of acute ventilatory failure, attempts are made to discontinue the ventilator (weaning). About 20% of weaning attempts fail, ultimately, because the respiratory controller is unable to sustain ventilation and this failure is signaled by development of rapid shallow breathing. Substantial advances in the medical management of acute ventilatory failure that requires ventilator assistance are most likely to result from research yielding novel insights into the operation of the respiratory control system. © 2012 American Physiological Society. Compr Physiol 2:2871‐2921, 2012.

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Figure 1. Figure 1.

The relationship between minute ventilation (E) and arterial carbon dioxide tension (PaCO2) in a healthy subject with a constant level of CO2 production (200 mL/min) and a dead space to tidal volume ratio of 0.40; this relationship is termed the metabolic hyperbola. Also shown is a normal normoxic ventilatory response to CO2 of 5 L/min/mmHg, the controller curve (dotted straight line). The set point of the system is determined by the intersection of the two relationships .

Figure 2. Figure 2.

Schematic representation of mechanisms that contribute to variable degrees of hypercapnia in patients with COPD who receive supplemental oxygen. Patient A has a baseline PaCO2 of 30 mmHg (green symbol) and a VD/VT of 0.40 (the lower black metabolic hyperbola). Administration of supplemental oxygen results in a 2‐L decrease in minute ventilation (blue symbol; represented as a vertical drop for the sake of simplicity). This patient has a normal CO2 controller response (slope of the red line, 1.0 L/min/mmHg), which brings his minute ventilation back up to the black hyperbola (red arrowhead). Consequently, administration of supplemental oxygen produces an increase in PCO2 of only 1.5 torr. Patient B also has a baseline VD/VT of 0.40, but his PCO2 is 50 mmHg (green symbol). Administration of supplemental oxygen again results in a 2‐L decrease in minute ventilation (blue symbol). This patient has a depressed CO2 controller response (slope of the red line, 0.2 L/min/mmHg), and administration of oxygen produces an increase in dead space from 0.40 to 0.60 secondary to worsening of ventilation‐perfusion relationships (consequent to release of hypoxic vasoconstriction and the development of CO2‐induced bronchodilation); the patient accordingly moves from the lower black metabolic hyperbola to the upper blue hyperbola. Consequently, administration of supplemental oxygen produces an increase in PCO2 of 15 torr (10‐fold greater than in Patient A).

Figure 3. Figure 3.

Schematic representation of the isovolume pressure‐flow relationship. Patients with COPD exhibit an initial diagonal segment, where increases in pressure produce increases in airflow (the effort‐dependent region on the left), followed by a flat portion, where increases in pressure do not produce increases in flow (the effort‐independent region on the right). Compared with a healthy subject, the slope of the initial diagonal segment is decreased, indicating an increase in airway resistance, and maximum flow is much reduced in the remaining portion as a result of expiratory flow limitation. [Modified, with permission, from Pride and Macklem .]

Figure 4. Figure 4.

Differing degrees of intrinsic positive end‐expiratory pressure (PEEP) in patients with COPD. Tracings are flow, airway pressure (Paw), and esophageal pressure (Pes) in two patients with COPD receiving assisted ventilation with pressure support set at 20 cmH2O (no external PEEP is applied). The patient on the left had a myocardial infarction complicated by congestive heart failure, and the patient on the right had sepsis. Intrinsic PEEP, estimated as the difference in esophageal pressure between the onset of inspiratory effort (vertical blue line) and the onset of inspiratory flow (vertical red line), was 0.5 cmH2O in the patient on the left and 10.6 cmH2O in the patient on the right. This method of estimating intrinsic PEEP is based on the assumption that the change in esophageal pressure reflects the inspiratory muscle pressure required to counterbalance the end‐expiratory elastic recoil of the respiratory system.

Figure 5. Figure 5.

Tracings of transdiaphragmatic pressure (Pdi) during bilateral phrenic nerve stimulation in a patient with COPD. During a forceful Mueller maneuver, stimulation produced a superimposed twitch pressure (arrow). On the right is a twitch pressure achieved by stimulation during resting breathing just after the Mueller maneuver. The ratio of the amplitude of superimposed twitch pressure to resting twitch pressure (expressed as a percentage) measures the extent that muscle is not recruited by the central nervous system during the Mueller maneuver. The extent of muscle recruitment is usually expressed as the voluntary activation index, which is calculated as: 100 minus the superimposed twitch pressure to resting twitch pressure ratio. In the displayed example, the amplitude of the superimposed twitch pressure is 19% of the amplitude of resting twitch pressure, yielding a voluntary activation index of 81%; if the superimposed stimulus had evoked no increase in pressure, the activation index would have been 100% . Of note, a twitch pressure recorded shortly after forceful contractions (potentiated twitch) is greater than a twitch pressure recorded after 15 to 20 min of rest (nonpotentiated twitch) . Nonpotentiated twitches are usually used to quantify diaphragmatic force output at rest, and changes in force following fatiguing protocols .

Figure 6. Figure 6.

Recordings of tidal volume (VT) and airway pressure (Paw) in patients receiving ventilator assistance with assist‐control ventilation (ACV), synchronized intermittent mandatory ventilation (SIMV), and pressure support ventilation (PSV). The ordinates and abscissae differ from one panel to the next because the tracings were recorded in three different patients. See text for details.

Figure 7. Figure 7.

Increase in elastic recoil and expiratory muscle recruitment during pressure support. Flow (inspiration directed upward), airway pressure (Paw), and esophageal pressure (Pes) in a patient receiving pressure‐support of 0 (upper left panel), 5 cmH2O (upper right panel), 10 cmH2O (lower left panel), and 20 cmH2O (lower right panel). As pressure support was increased from 0 to 20 cmH2O, respiratory frequency decreased from 20 to 13 breaths/min and tidal swings in esophageal pressure decreased from 20 to 10 cmH2O. End‐inspiratory esophageal pressure returned to preinspiratory values at pressure support of 0, whereas the end‐inspiratory value was higher than preinspiratory esophageal pressure at pressure support of 20, suggesting recruitment of expiratory muscles and increased elastic recoil. The increase in airway pressure above the preset level (best seen at pressure support of 5 and 10) probably resulted from relaxation of the inspiratory muscles while mechanical inflation was still active; the extent of expiratory muscle contribution to the increase in airway pressure cannot be determined in the absence of measurements of chest‐wall recoil pressure. The flow signal at the start of inhalation demonstrates an initial spike that increases as the level of support increases; this phenomenon reflects the need for higher flows to achieve the higher target airway pressures.

Figure 8. Figure 8.

Recordings of flow, airway pressure (Paw), and transversus abdominis electromyography (EMG) in a critically ill patient with COPD receiving pressure support of 20 cmH2O. The onset of expiratory muscle activity (vertical dotted line) occurred when mechanical inflation was only partly completed. [From Parthasarathy S, Jubran A, Tobin MJ. Cycling of inspiratory‐ and expiratory‐muscle groups with the ventilator in airflow limitation. Am J Respir Crit Care Med 1998; 158: 1471‐1478 .]

Figure 9. Figure 9.

Schematic representation of the “dogleg” or “hockey‐stick” configuration of the ventilatory response to CO2 during wakefulness. At alveolar carbon dioxide tension (PACO2) levels above eupnea, minute ventilation increases linearly in proportion to increases in PACO2. At PACO2 levels below eupnea, the ventilatory response gradually decreases and becomes essentially flat. [Based on data presented by Nielsen M, Smith H. Studies on the regulation of respiration in acute hypoxia. Acta Physiol Scand 1952; 24: 293‐313 .]

Figure 10. Figure 10.

Contrasting response of respiratory motor output and respiratory frequency over a 15 mmHg variation in PCO2. Average responses of change in respiratory motor output, quantified as change in pressure over time (dP/dt), and change in respiratory frequency in response to changes in end‐tidal carbon dioxide tension (PETCO2) from about 26 to 41 mmHg. Respiratory motor output increased progressively in response to increases in PETCO2, even at hypocapnic levels, whereas the response of respiratory frequency to change in PETCO2 was very weak or absent in the hypocapnic range and increased significantly only when PETCO2 exceeded 36 mmHg. [Adapted, with permission, from Patrick et al. .]

Figure 11. Figure 11.

Limited decreases in respiratory frequency in response to increases in ventilator tidal volume. Individual changes in respiratory frequency (left panel) and minute ventilation (right panel) in healthy subjects as tidal volume was increased from a minimum to a maximum setting during assist‐control ventilation, resulting in tidal volumes of 944 ± 198 and 1867 ± 277 (SD) mL, respectively. The average respiratory frequency and minute ventilation at the minimum and maximum tidal volume settings are listed below the horizontal axes. Doubling of delivered tidal volumes produced minimal decreases (∼12%) in respiratory frequency. [Adapted, with permission, from Puddy et al. .]

Figure 12. Figure 12.

Polysomnographic tracings during assist‐control ventilation and pressure support in a representative patient. Electroencephalogram (C4‐A1, O3‐A2), electrooculogram (ROC, LOC), electromyograms (Chin and Leg), integrated tidal volume (VT), rib‐cage (RC), and abdominal (AB) excursions on respiratory inductive plethysmography are shown. Arousals and awakenings, indicated by horizontal bars, were more numerous during pressure support than during assist‐control ventilation. [Adapted, with permission, from Parthasarathy S and Tobin MJ. Effect of ventilator mode on sleep quality in critically ill patients. Am J Respir Crit Care Med 166: 1423‐1429, 2002 .]

Figure 13. Figure 13.

The difference between the average end‐tidal CO2 and the apnea threshold plotted against the number of central apneas per hour of pressure support alone (closed symbols) and pressure support with added dead space (open symbols) in six patients. The average end‐tidal CO2 was measured during both sleep and wakefulness. The mean number of central apneas per hour was strongly correlated with the end‐tidal CO2 during a mixture of both sleep and wakefulness (including the transitions between sleep and wakefulness) (r = −0.83, P < 0.001). [Adapted, with permission, from Parthasarathy S and Tobin MJ. Effect of ventilator mode on sleep quality in critically ill patients. Am J Respir Crit Care Med 166: 1423‐1429, 2002 .]

Figure 14. Figure 14.

Three points at which patient‐ventilator dysynchrony may arise: point of triggering (cycling‐on function), inspiratory flow delivery (posttrigger inflation), and the point of switchover between inspiration and expiration (cycling‐off function). Each is discussed in the text.

Figure 15. Figure 15.

Patient effort related to ventilator triggering. Tracings of flow, airway pressure (Paw), and esophageal pressure (Pes) in a patient receiving the volume‐cycled form of assist‐control ventilation. The vertical blue line represents the onset of patient inspiratory effort, the vertical red line represents the onset of flow delivery (opening of the ventilator valve), and the vertical green line represents the transition from inspiratory flow to expiratory flow; the dashed tracing above the Pes recording on the bottom panel is an estimate of the patient's chest‐wall recoil pressure, measured during passive ventilation. The effort of triggering is divided into two phases. First, the effort of the trigger phase (single hatched area). Second, the effort of the posttrigger phase (double hatched area) is the area enclosed between esophageal pressure and estimated chest‐wall recoil pressure between the onset of flow delivery and the switch from inspiratory flow to expiratory flow.

Figure 16. Figure 16.

Patient effort during the time that the ventilator is delivering a breath (measured as inspiratory pressure‐time product per breath in cmH2O.s) is closely related to a patient's respiratory motor output (measured as dP/dt in cmH2O.s) at the moment that a patient triggers the ventilator (r = 0.78). The inspiratory muscles of a patient who has a low respiratory drive at the time of triggering the ventilator will perform very little work during the remainder of inspiration when the ventilator is providing assistance. Conversely, the inspiratory muscles of a patient who has a high respiratory drive will expend considerable effort throughout the period of inspiration even though the mechanical ventilator is providing assistance. [Based on data published in Leung P, Jubran A and Tobin MJ. Comparison of assisted ventilator modes on triggering, patient effort, and dyspnea. Am J Respir Crit Care Med 155: 1940‐1948, 1997 .]

Figure 17. Figure 17.

Graded increases in pressure support produced a decrease in total pressure‐time product (PTP) per breath (closed symbols), whereas PTP during the trigger phase (open symbols) did not change (left panel). The constancy of PTP during triggering probably resulted from different factors becoming operational at different levels of assistance (right panel). At low levels of pressure support, respiratory motor output (dP/dt) and intrinsic positive end‐expiratory pressure (PEEPi) were high but triggering time was short, resulting in a large change in pleural pressure over a brief interval. At high levels of pressure support, dP/dt and PEEPi were low but triggering time was long, resulting in a smaller change in pleural pressure over a longer time. [Adapted, with permission, from Leung P, Jubran A and Tobin MJ. Comparison of assisted ventilator modes on triggering, patient effort, and dyspnea. Am J Respir Crit Care Med 155: 1940‐1948, 1997 .]

Figure 18. Figure 18.

Estimations of the duration of neural inspiratory time. Representative tracings of the raw crural diaphragmatic electromyogram (Edi), the processed Edi achieved by removing electrocardiography (EKG) artifacts by computer, the moving average (MA) of the processed Edi, esophageal pressure (Pes), and flow in a patient breathing spontaneously. The relationship between an indirect estimate of the onset of neural inspiratory time and its onset on the diaphragmatic EMG signal was assessed by calculation of the phase angle, expressed in degrees. In this example, the onset of inspiratory time is estimated as occurring earlier (negative phase angle of 15°) by esophageal pressure‐based measurements and later (positive phase angle of 110°) by flow‐based measurements. The duration of inspiratory time as estimated by esophageal pressure (hatched horizontal bar) is longer than the true inspiratory time measured by diaphragmatic electromyogram (note that the hatched bar is wider than 0‐360° on the solid black bar of the reference measurement). The duration of inspiratory time as estimated by flow‐based measurements is shorter (clear horizontal bar) than the true inspiratory time measured by diaphragmatic electromyogram (note that the open white bar is narrower than 0‐360° on the solid black bar of the reference measurement). [Adapted, with permission, from Parthasarathy S, Jubran A and Tobin MJ. Assessment of neural inspiratory time in ventilator‐supported patients. Am J Respir Crit Care Med 162: 546‐552, 2000 .]

Figure 19. Figure 19.

The phase angle between the indirect estimate of the onset of neural inspiratory time and its reference measurement in five patients during mechanical ventilation; estimates from the esophageal pressure (Pes) tracings are shown as closed squares, estimates from flow tracings are shown as closed circles, and estimates from transdiaphragmatic pressure (Pdi) tracings are shown as closed triangles. The closed symbols represent the mean difference (bias) in phase angle; the open symbols to the right of each closed symbol represent the mean difference between the two measurements noted during the reproducibility testing of the reference measurement. The error bars represent ±2 SD (twice the precision). A positive phase angle indicates a delay in the onset of neural inspiratory time for the flow‐based measurements. [Modified, with permission, from Parthasarathy S, Jubran A and Tobin MJ. Assessment of neural inspiratory time in ventilator‐supported patients. Am J Respir Crit Care Med 162: 546‐552, 2000 .]

Figure 20. Figure 20.

Failure to trigger the ventilator. Flow, airway pressure (Paw) and esophageal pressure (Pes) in a patient with COPD who is receiving assist‐control ventilation at the following settings: tidal volume 600 mL, inspiratory flow 60 L/min, trigger sensitivity −2 cmH2O and positive end‐expiratory pressure 0 cmH2O. The patient's intrinsic respiratory rate is 28 breaths/min, whereas the number of breaths delivered by the ventilator is 16 breaths/min. That is, 43% of the patient's inspiratory efforts fail to trigger ventilator assistance. Contractions of the inspiratory muscles during the failed triggering attempts cause a temporary deceleration of expiratory flow and much less obvious decreases in airway pressure. The temporary decelerations in expiratory flow are followed by temporary accelerations of expiratory flow that coincide with the termination of the unsuccessful inspiratory effort.

Figure 21. Figure 21.

The concordance between neural expiratory time and mechanical expiratory time can be quantified in terms of the phase angle, expressed in degrees. If neural activity begins simultaneously with the machine, the phase angle (θ) is zero. Neural activity beginning after the offset of mechanical inflation results in a positive phase angle (60° for Subject 1). Neural activity beginning before the onset of mechanical inflation results in a negative phase angle (−45° for Subject 2). [Adapted, with permission, from Parthasarathy S, Jubran A and Tobin MJ. Cycling of inspiratory and expiratory muscle groups with the ventilator in airflow limitation. Am J Respir Crit Care Med 158: 1471‐1478, 1998 .]

Figure 22. Figure 22.

Phase angle between neural and mechanical expiratory times before triggering (closed circles) and nontriggering (open circles) attempts. At pressure support (PS) of 10 and 20 cmH2O, the phase angle before nontriggering attempts exceeded that before triggering attempts, indicating that neural expiratory time during late mechanical inflation was longer before nontriggering attempts than before triggering attempts (for pressure support 10, P = 0.0002; for pressure support 20, P = 0.01). [Adapted, with permission, from Parthasarathy S, Jubran A and Tobin MJ. Cycling of inspiratory and expiratory muscle groups with the ventilator in airflow limitation. Am J Respir Crit Care Med 158: 1471‐1478, 1998 .]

Figure 23. Figure 23.

Four incidents of double triggering, each indicated by an arrowhead symbol (↑). Airway pressure (Paw) and esophageal pressure (Pes) in a patient with COPD and pneumonia who was receiving assist‐control ventilation at the following settings: tidal volume 600 mL, inspiratory flow 60 L/min, trigger sensitivity −2 cmH2O and positive end‐expiratory pressure 5 cmH2O. The duration of neural inhalation of the double‐triggered breaths, roughly equivalent to the width of the associated swings in esophageal pressure, was substantially longer than the neural inhalation of the normally triggered breaths.

Figure 24. Figure 24.

Volume stacking caused by double triggering. Flow (top panel), volume (middle panel), and esophageal pressure (lower panel) in a patient with COPD receiving assist‐control ventilation. During first breath, esophageal pressure remains positive indicating that the patient did not trigger the inflation. During the second breath, esophageal pressure becomes negative indicating active inspiratory effort, which lasts more than 1 s; the duration of mechanical inflation is 0.6 s. The longer duration of neural inspiration as compared with mechanical inflation causes the ventilator to deliver a second breath before there is time for exhalation. As a result, end‐inspiratory lung volume increases (breath stacking) with a consequent increase in elastic recoil. The increase in elastic recoil is responsible for the higher peak expiratory flow on the second breath as compared with the first breath.

Figure 25. Figure 25.

Influence of ventilator flow setting on patient effort. Flow (inspiration directed upward), airway pressure (Paw), and esophageal pressure (Pes) in a patient with respiratory failure who is receiving assist‐control ventilation; inspiratory flow is set at 60 L/min in the left panel and at 90 L/min in the right panel. At an inspiratory flow of 60 L/min (left panel), the pronounced negative deflection in airway pressure (patient effort to trigger the ventilator) together with subsequent extensive scalloping signifies that the inspiratory flow delivered by the ventilator is insufficient to meet the high demand. At an inspiratory flow of 90 L/min (right panel), the small negative deflection in airway pressure together with the subsequent smooth convex contour signifies that the delivered flow satisfies the patient's respiratory drive. Accordingly, the flow of 90 L/min achieved greater unloading of the respiratory muscles, as signaled by the shorter duration of inspiratory effort and the smaller swings in esophageal pressure.

Figure 26. Figure 26.

Continuous recordings of flow, esophageal pressure (Pes), and the sum of rib‐cage and abdominal motion in a patient with COPD receiving assist‐control ventilation at a constant tidal volume. As flow increased from 30 to 60 and 90 L/min (from right to left; i.e., the opposite of the usual presentation), frequency increased (from 18 to 23 and 26 breaths/min, respectively), PEEPi decreased (from 15.6 to 14.4 and 13.3 cmH2O, respectively), and end‐expiratory lung volume also fell. Increases in flow from 30 L/ min to 60 and 90 L/min also led to decreases in the swings in Pes from 21.5 to 19.5 and 16.8 cmH2O, respectively. [Adapted, with permission, from Laghi F, Segal J, Choe WK and Tobin MJ. Effect of imposed inflation time on respiratory frequency and hyperinflation in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 163: 1365‐1370, 2001 .]

Figure 27. Figure 27.

Changes in pressure‐time product (PTP) per minute (left panel), PTP per breath (middle panel), and frequency (right panel) as the level of intermittent mandatory ventilation (IMV) and pressure support (PS) were progressively increased in 11 ventilator‐dependent patients. Ventilator assistance of 0% represents unassisted breathing; PS of 100% represents the level necessary to achieve a tidal volume equivalent to that during assist‐control ventilation (10 mL/kg); IMV of 100% is the same ventilator rate as during assist‐control ventilation. The left panel shows that the rate of change in PTP per minute over the entire span of assistance did not differ between PS and IMV. The middle panel shows that the rate of change in PTP per breath decreased linearly as the rate of IMV was increased; the decrease with PS was linear only up a medium level and decreased little thereafter. The right panel shows that respiratory frequency decreased linearly as PS was increased, whereas it changed little with IMV until a high level of assistance was provided. See text for interpretation. [Based on data from Leung P, Jubran A and Tobin MJ. Comparison of assisted ventilator modes on triggering, patient effort, and dyspnea. Am J Respir Crit Care Med 155: 1940‐1948, 1997 .]

Figure 28. Figure 28.

Expiratory activity during mechanical inflation. Flow, airway pressure (Paw) and esophageal pressure (Pes) in a patient with COPD who is receiving assist‐control ventilation. The patient's first two inspiratory efforts (red vertical lines) trigger the ventilator successfully. The third and fourth inspiratory efforts are very weak (arrows) and do not trigger a mechanical inflation. The last inspiratory effort triggers the ventilator, and at the end of this mechanical inflation (blue vertical line) the patient recruits his expiratory muscles, producing an increase in esophageal pressure above the expected elastic recoil of the lung (dashed tracing) before the termination of mechanical inflation. Expiratory muscle recruitment produces a transient cessation of expiratory flow, which corresponds to a transient increase in esophageal pressure to approximately 20 cmH2O.

Figure 29. Figure 29.

Breath‐to‐breath values of tidal volume during 1 h of resting breathing in a patient with restrictive lung disease (top panel) and in a healthy control subject (bottom panel). The coefficient of variation for tidal volume in the patient (0.13) was more than five times smaller than that in the healthy subject (0.72). [Adapted, with permission, from Brack T, Jubran A and Tobin MJ. Dyspnea and decreased variability of breathing in patients with restrictive lung disease. Am J Respir Crit Care Med 165: 1260‐1264, 2002 .]

Figure 30. Figure 30.

Variability of breathing. Time series of airflow and esophageal pressure in a patient with acute respiratory failure secondary to an acute exacerbation of COPD who is being ventilated with pressure support of 5 cmH2O (PEEP, 0 cmH2O). The esophageal‐pressure tracing exhibits wandering values at end‐expiration and varying inspiratory excursions; these features are somewhat less evident on the flow tracing.

Figure 31. Figure 31.

The mean respiratory cycle during spontaneous breathing in seven weaning‐failure and ten weaning‐success patients. The early termination of inspiratory time in the weaning‐failure patients leads to a decrease in tidal volume. The decrease in inspiratory time, coupled with a decrease in expiratory time, results in a faster respiratory frequency. Bars represent 1 SE. [Adapted, with permission, from Tobin MJ, et al. The pattern of breathing during successful and unsuccessful trials of weaning from mechanical ventilation. Am Rev Respir Dis 134: 1111‐1118, 1986 .]

Figure 32. Figure 32.

A time‐series, breath‐by‐breath plot of respiratory frequency and tidal volume in a patient who failed a weaning trial. The arrow indicates the point of resuming spontaneous breathing. Rapid, shallow breathing developed almost immediately after discontinuation of the ventilator. [Adapted, with permission, from Tobin MJ, et al. The pattern of breathing during successful and unsuccessful trials of weaning from mechanical ventilation. Am Rev Respir Dis 134: 1111‐1118, 1986 .]

Figure 33. Figure 33.

The relationship between work of breathing and the frequency‐tidal volume (f/VT) ratio for a constant alveolar ventilation of 4 L/min based on the model of Otis and collaborators . Work of breathing is least for f/VT ratios of 37 to 59; it increases exponentially as f/VT increases from 59 to 234/min/L. [Adapted, with permission, from Tobin MJ, Laghi F and Brochard L. Role of the respiratory muscles in acute respiratory failure of COPD: lessons from weaning failure. J Appl Physiol 107: 962‐970, 2009 .]

Figure 34. Figure 34.

Two superimposed Campbell diagrams of work of breathing in a patient at the start and end of a trial of spontaneous breathing. Over the course of the weaning trial, the patient developed an increase in PaCO2 from 48 to 73 mmHg, but minimal change in overall work of breathing, suggesting that the hypoventilation resulted from either failure of respiratory motor output to increase during the weaning trial or an inability of the respiratory controller to sense the rise in PaCO2.

Figure 35. Figure 35.

Inspiratory resistance of the lung (Rinsp,L), dynamic lung elastance (Edyn,L), and intrinsic positive end‐expiratory pressure (PEEPi) in 17 weaning‐failure patients and 14 weaning‐success patients. Data displayed were obtained during the second and last minute of a T‐tube trial, and at one third and two‐thirds of the trial duration. Between the onset and end of the trial, the failure group developed increases in Rinsp,L (P < 0.009), Edyn,L (P < 0.0001), and PEEPi (P < 0.0001) and the success group developed increases in Edyn,L (P < 0.006) and PEEPi (P < 0.02). Over the course of the trial, the failure group had higher values of Rinsp,L (P < 0.003), Edyn,L (P < 0.006), and PEEPi (P < 0.009) than the success group [Adapted, with permission, from Jubran A and Tobin MJ. Pathophysiologic basis of acute respiratory distress in patients who fail a trial of weaning from mechanical ventilation. Am J Respir Crit Care Med 155: 906‐915, 1997 .]

Figure 36. Figure 36.

Respiratory effort during a weaning trial. Recordings of flow (inspiration directed upward) and esophageal pressure (Pes) in a patient with severe COPD who failed a weaning trial (left panel) and in a weaning‐success patient, who had been intubated because of an opiate overdose (and had no lung disease) (right panel), 10 min into a trial of spontaneous breathing. The weaning‐failure patient exhibits a steeper fall and greater excursion in esophageal pressure than did the weaning‐success patient—features that signify greater respiratory motor output. Despite the threefold larger excursion in esophageal pressure in the weaning‐failure patient, peak inspiratory flow in this patient is only twice as great as in the weaning‐success patient, signifying more abnormal mechanics in the weaning‐failure patient. The duration of respiratory cycle was shorter in weaning‐failure patient signifying tachypnea. The expiratory flow in the weaning‐failure patient demonstrates a supramaximal flow transient at the beginning of exhalation that is typical of expiratory flow limitation.

Figure 37. Figure 37.

Progressive increase in inspiratory effort in a weaning‐failure patient. Flow (top panel), esophageal pressure (Pes, middle panel), and airway pressure (Paw, lower panel) in a patient who developed severe respiratory distress while receiving continuous positive airway pressure (CPAP) of 5 cmH2O. The patient had developed respiratory failure (requiring mechanical ventilation) after developing a pulmonary embolus subsequent to undergoing lobectomy for lung cancer. The swings in esophageal pressure became progressively more negative over the first 30 s of the trial.

Figure 38. Figure 38.

Time‐series plot of swings in esophageal pressure (Pes; left panel) and frequency‐to‐tidal volume ratio (f/VT; right panel) during a trial of spontaneous breathing in a weaning‐failure patient. Black dots represent 1‐min averages. The solid line indicates the average value of Pes swings and f/VT of the final minute of the trial. The dashed lines indicate ±10% of the final minute values of Pes swings and f/VT. The time taken to reach ±10% of the final value was 14 min for Pes swings and 2 min for f/VT. [Adapted, with permission, from Jubran A, et al. Weaning prediction: esophageal pressure monitoring complements readiness testing. Am J Respir Crit Care Med 171: 1252‐1259, 2005 .]

Figure 39. Figure 39.

Esophageal pressure (Pes), gastric pressure (Pga), transdiaphragmatic pressure (Pdi), and compound motor action potential (CAMP) of the right and left hemidiaphragm after phrenic nerve stimulation before (left) and after (right) a T‐tube trial in a weaning failure patient. The end‐expiratory value of Pes and the amplitude of the right and left CAMPs were the same before and after the trial, indicating that the stimulations were delivered at the same lung volume and that the stimulations achieved the same extent of diaphragmatic recruitment. The amplitude of twitch Pdi elicited by phrenic nerve stimulation was the same before and after weaning. [Adapted, with permission, from Laghi F, et al. Is weaning failure caused by low‐frequency fatigue of the diaphragm? Am J Respir Crit Care Med 167: 120‐127, 2003 .]

Figure 40. Figure 40.

Interrelationship between the duration of a spontaneous breathing trial, tension‐time index of the diaphragm, and predicted time to task failure in nine patients who failed a trial of weaning from mechanical ventilation. The patients breathed spontaneously for an average of 44 min before a physician terminated the trial. At the start of the trial, the tension‐time index was 0.17, and the formula of Bellemare and Grassino (see text for details) predicted that patients could sustain spontaneous breathing for another 59 min before developing task failure. As the trial progressed, the tension‐time index increased and the predicted time to development of task failure decreased. At the end of the trial, the tension‐time index reached 0.26. That patients were predicted to sustain spontaneous breathing for another 13 min before developing task failure clarifies why patients did not develop a decrease in diaphragmatic twitch pressure. In other words, physicians interrupted the trial on the basis of clinical manifestations of respiratory distress, before patients had sufficient time to develop contractile fatigue. [Adapted, with permission, from Laghi F, Tobin MJ: Disorders of the respiratory muscles. Am J Respir Crit Care Med 2003; 168:10 .]

Figure 41. Figure 41.

Expiratory rise in gastric pressure (Pga) during the course of a weaning trial in failure () and success patients (). Between the onset and the end of the trial, increases in expiratory rise in Pga (P = 0.0005) occurred in failure patients but not in the success patients. Over the course of the trial, failure patients had higher values of expiratory rise in Pga (P = 0.004) than success patients. Bars represent ± SE. [Modified, with permission, from Parthasarathy S, Jubran A, Laghi F and Tobin MJ. Sternomastoid, rib‐cage and expiratory muscle activity during weaning failure. J Appl Physiol 103: 140‐147, 2007 .]

Figure 42. Figure 42.

Representative tracings of flow, Pes, and EMGscm in a weaning‐failure patient. Recordings were obtained during the first minute of the weaning trial, 40% of trial duration, and last minute of the trial. Phasic inspiratory activity of the sternomastoid muscle was evident within the first minute of the trial, and it increased progressively over the course of the trial. Note that phasic activity of the sternomastoids persists into expiration. [Adapted, with permission, from Parthasarathy S, Jubran A, Laghi F and Tobin MJ. Sternomastoid, rib‐cage and expiratory muscle activity during weaning failure. J Appl Physiol 103: 140‐147, 2007 .]

Figure 43. Figure 43.

Plots of tidal changes in esophageal pressure (ΔPes) against tidal changes in gastric pressure (ΔPga) in a weaning‐success patient and a weaning‐failure patient. At the start of a weaning trial, the success patient (top left panel) exhibited swings in esophageal pressure that became markedly more negative between the onset (closed symbol) and the end of inspiration (open symbol); in contrast, gastric pressure increased only slightly. Therefore, the slope of the PesPga plot at the onset of weaning (top left panel) was much greater than the slope recorded in healthy subjects during resting breathing, where the tidal change in gastric pressure is often greater than the tidal change in esophageal pressure. The steep PesPga plot (top left panel) indicates a greater‐than‐usual contribution of the rib‐cage muscles to tidal breathing than that of the diaphragm. Between the onset (top left panel) and the end of weaning (top right panel), the slope of the PesPga plot changed very little, indicating a constant contribution of the diaphragm and rib‐cage muscles to tidal breathing over the course of the weaning trial. In the case of the weaning‐failure patient, the inspiratory swings in esophageal pressure and gastric pressure had a similar pattern at the start of the trial to that in the success patient (bottom left panel). At the end of the trial, the failure patient exhibited a markedly negative slope in the PesPga plot, signifying a further increase in inspiratory rib‐cage muscle recruitment that was out of proportion to diaphragmatic recruitment.



Figure 1.

The relationship between minute ventilation (E) and arterial carbon dioxide tension (PaCO2) in a healthy subject with a constant level of CO2 production (200 mL/min) and a dead space to tidal volume ratio of 0.40; this relationship is termed the metabolic hyperbola. Also shown is a normal normoxic ventilatory response to CO2 of 5 L/min/mmHg, the controller curve (dotted straight line). The set point of the system is determined by the intersection of the two relationships .



Figure 2.

Schematic representation of mechanisms that contribute to variable degrees of hypercapnia in patients with COPD who receive supplemental oxygen. Patient A has a baseline PaCO2 of 30 mmHg (green symbol) and a VD/VT of 0.40 (the lower black metabolic hyperbola). Administration of supplemental oxygen results in a 2‐L decrease in minute ventilation (blue symbol; represented as a vertical drop for the sake of simplicity). This patient has a normal CO2 controller response (slope of the red line, 1.0 L/min/mmHg), which brings his minute ventilation back up to the black hyperbola (red arrowhead). Consequently, administration of supplemental oxygen produces an increase in PCO2 of only 1.5 torr. Patient B also has a baseline VD/VT of 0.40, but his PCO2 is 50 mmHg (green symbol). Administration of supplemental oxygen again results in a 2‐L decrease in minute ventilation (blue symbol). This patient has a depressed CO2 controller response (slope of the red line, 0.2 L/min/mmHg), and administration of oxygen produces an increase in dead space from 0.40 to 0.60 secondary to worsening of ventilation‐perfusion relationships (consequent to release of hypoxic vasoconstriction and the development of CO2‐induced bronchodilation); the patient accordingly moves from the lower black metabolic hyperbola to the upper blue hyperbola. Consequently, administration of supplemental oxygen produces an increase in PCO2 of 15 torr (10‐fold greater than in Patient A).



Figure 3.

Schematic representation of the isovolume pressure‐flow relationship. Patients with COPD exhibit an initial diagonal segment, where increases in pressure produce increases in airflow (the effort‐dependent region on the left), followed by a flat portion, where increases in pressure do not produce increases in flow (the effort‐independent region on the right). Compared with a healthy subject, the slope of the initial diagonal segment is decreased, indicating an increase in airway resistance, and maximum flow is much reduced in the remaining portion as a result of expiratory flow limitation. [Modified, with permission, from Pride and Macklem .]



Figure 4.

Differing degrees of intrinsic positive end‐expiratory pressure (PEEP) in patients with COPD. Tracings are flow, airway pressure (Paw), and esophageal pressure (Pes) in two patients with COPD receiving assisted ventilation with pressure support set at 20 cmH2O (no external PEEP is applied). The patient on the left had a myocardial infarction complicated by congestive heart failure, and the patient on the right had sepsis. Intrinsic PEEP, estimated as the difference in esophageal pressure between the onset of inspiratory effort (vertical blue line) and the onset of inspiratory flow (vertical red line), was 0.5 cmH2O in the patient on the left and 10.6 cmH2O in the patient on the right. This method of estimating intrinsic PEEP is based on the assumption that the change in esophageal pressure reflects the inspiratory muscle pressure required to counterbalance the end‐expiratory elastic recoil of the respiratory system.



Figure 5.

Tracings of transdiaphragmatic pressure (Pdi) during bilateral phrenic nerve stimulation in a patient with COPD. During a forceful Mueller maneuver, stimulation produced a superimposed twitch pressure (arrow). On the right is a twitch pressure achieved by stimulation during resting breathing just after the Mueller maneuver. The ratio of the amplitude of superimposed twitch pressure to resting twitch pressure (expressed as a percentage) measures the extent that muscle is not recruited by the central nervous system during the Mueller maneuver. The extent of muscle recruitment is usually expressed as the voluntary activation index, which is calculated as: 100 minus the superimposed twitch pressure to resting twitch pressure ratio. In the displayed example, the amplitude of the superimposed twitch pressure is 19% of the amplitude of resting twitch pressure, yielding a voluntary activation index of 81%; if the superimposed stimulus had evoked no increase in pressure, the activation index would have been 100% . Of note, a twitch pressure recorded shortly after forceful contractions (potentiated twitch) is greater than a twitch pressure recorded after 15 to 20 min of rest (nonpotentiated twitch) . Nonpotentiated twitches are usually used to quantify diaphragmatic force output at rest, and changes in force following fatiguing protocols .



Figure 6.

Recordings of tidal volume (VT) and airway pressure (Paw) in patients receiving ventilator assistance with assist‐control ventilation (ACV), synchronized intermittent mandatory ventilation (SIMV), and pressure support ventilation (PSV). The ordinates and abscissae differ from one panel to the next because the tracings were recorded in three different patients. See text for details.



Figure 7.

Increase in elastic recoil and expiratory muscle recruitment during pressure support. Flow (inspiration directed upward), airway pressure (Paw), and esophageal pressure (Pes) in a patient receiving pressure‐support of 0 (upper left panel), 5 cmH2O (upper right panel), 10 cmH2O (lower left panel), and 20 cmH2O (lower right panel). As pressure support was increased from 0 to 20 cmH2O, respiratory frequency decreased from 20 to 13 breaths/min and tidal swings in esophageal pressure decreased from 20 to 10 cmH2O. End‐inspiratory esophageal pressure returned to preinspiratory values at pressure support of 0, whereas the end‐inspiratory value was higher than preinspiratory esophageal pressure at pressure support of 20, suggesting recruitment of expiratory muscles and increased elastic recoil. The increase in airway pressure above the preset level (best seen at pressure support of 5 and 10) probably resulted from relaxation of the inspiratory muscles while mechanical inflation was still active; the extent of expiratory muscle contribution to the increase in airway pressure cannot be determined in the absence of measurements of chest‐wall recoil pressure. The flow signal at the start of inhalation demonstrates an initial spike that increases as the level of support increases; this phenomenon reflects the need for higher flows to achieve the higher target airway pressures.



Figure 8.

Recordings of flow, airway pressure (Paw), and transversus abdominis electromyography (EMG) in a critically ill patient with COPD receiving pressure support of 20 cmH2O. The onset of expiratory muscle activity (vertical dotted line) occurred when mechanical inflation was only partly completed. [From Parthasarathy S, Jubran A, Tobin MJ. Cycling of inspiratory‐ and expiratory‐muscle groups with the ventilator in airflow limitation. Am J Respir Crit Care Med 1998; 158: 1471‐1478 .]



Figure 9.

Schematic representation of the “dogleg” or “hockey‐stick” configuration of the ventilatory response to CO2 during wakefulness. At alveolar carbon dioxide tension (PACO2) levels above eupnea, minute ventilation increases linearly in proportion to increases in PACO2. At PACO2 levels below eupnea, the ventilatory response gradually decreases and becomes essentially flat. [Based on data presented by Nielsen M, Smith H. Studies on the regulation of respiration in acute hypoxia. Acta Physiol Scand 1952; 24: 293‐313 .]



Figure 10.

Contrasting response of respiratory motor output and respiratory frequency over a 15 mmHg variation in PCO2. Average responses of change in respiratory motor output, quantified as change in pressure over time (dP/dt), and change in respiratory frequency in response to changes in end‐tidal carbon dioxide tension (PETCO2) from about 26 to 41 mmHg. Respiratory motor output increased progressively in response to increases in PETCO2, even at hypocapnic levels, whereas the response of respiratory frequency to change in PETCO2 was very weak or absent in the hypocapnic range and increased significantly only when PETCO2 exceeded 36 mmHg. [Adapted, with permission, from Patrick et al. .]



Figure 11.

Limited decreases in respiratory frequency in response to increases in ventilator tidal volume. Individual changes in respiratory frequency (left panel) and minute ventilation (right panel) in healthy subjects as tidal volume was increased from a minimum to a maximum setting during assist‐control ventilation, resulting in tidal volumes of 944 ± 198 and 1867 ± 277 (SD) mL, respectively. The average respiratory frequency and minute ventilation at the minimum and maximum tidal volume settings are listed below the horizontal axes. Doubling of delivered tidal volumes produced minimal decreases (∼12%) in respiratory frequency. [Adapted, with permission, from Puddy et al. .]



Figure 12.

Polysomnographic tracings during assist‐control ventilation and pressure support in a representative patient. Electroencephalogram (C4‐A1, O3‐A2), electrooculogram (ROC, LOC), electromyograms (Chin and Leg), integrated tidal volume (VT), rib‐cage (RC), and abdominal (AB) excursions on respiratory inductive plethysmography are shown. Arousals and awakenings, indicated by horizontal bars, were more numerous during pressure support than during assist‐control ventilation. [Adapted, with permission, from Parthasarathy S and Tobin MJ. Effect of ventilator mode on sleep quality in critically ill patients. Am J Respir Crit Care Med 166: 1423‐1429, 2002 .]



Figure 13.

The difference between the average end‐tidal CO2 and the apnea threshold plotted against the number of central apneas per hour of pressure support alone (closed symbols) and pressure support with added dead space (open symbols) in six patients. The average end‐tidal CO2 was measured during both sleep and wakefulness. The mean number of central apneas per hour was strongly correlated with the end‐tidal CO2 during a mixture of both sleep and wakefulness (including the transitions between sleep and wakefulness) (r = −0.83, P < 0.001). [Adapted, with permission, from Parthasarathy S and Tobin MJ. Effect of ventilator mode on sleep quality in critically ill patients. Am J Respir Crit Care Med 166: 1423‐1429, 2002 .]



Figure 14.

Three points at which patient‐ventilator dysynchrony may arise: point of triggering (cycling‐on function), inspiratory flow delivery (posttrigger inflation), and the point of switchover between inspiration and expiration (cycling‐off function). Each is discussed in the text.



Figure 15.

Patient effort related to ventilator triggering. Tracings of flow, airway pressure (Paw), and esophageal pressure (Pes) in a patient receiving the volume‐cycled form of assist‐control ventilation. The vertical blue line represents the onset of patient inspiratory effort, the vertical red line represents the onset of flow delivery (opening of the ventilator valve), and the vertical green line represents the transition from inspiratory flow to expiratory flow; the dashed tracing above the Pes recording on the bottom panel is an estimate of the patient's chest‐wall recoil pressure, measured during passive ventilation. The effort of triggering is divided into two phases. First, the effort of the trigger phase (single hatched area). Second, the effort of the posttrigger phase (double hatched area) is the area enclosed between esophageal pressure and estimated chest‐wall recoil pressure between the onset of flow delivery and the switch from inspiratory flow to expiratory flow.



Figure 16.

Patient effort during the time that the ventilator is delivering a breath (measured as inspiratory pressure‐time product per breath in cmH2O.s) is closely related to a patient's respiratory motor output (measured as dP/dt in cmH2O.s) at the moment that a patient triggers the ventilator (r = 0.78). The inspiratory muscles of a patient who has a low respiratory drive at the time of triggering the ventilator will perform very little work during the remainder of inspiration when the ventilator is providing assistance. Conversely, the inspiratory muscles of a patient who has a high respiratory drive will expend considerable effort throughout the period of inspiration even though the mechanical ventilator is providing assistance. [Based on data published in Leung P, Jubran A and Tobin MJ. Comparison of assisted ventilator modes on triggering, patient effort, and dyspnea. Am J Respir Crit Care Med 155: 1940‐1948, 1997 .]



Figure 17.

Graded increases in pressure support produced a decrease in total pressure‐time product (PTP) per breath (closed symbols), whereas PTP during the trigger phase (open symbols) did not change (left panel). The constancy of PTP during triggering probably resulted from different factors becoming operational at different levels of assistance (right panel). At low levels of pressure support, respiratory motor output (dP/dt) and intrinsic positive end‐expiratory pressure (PEEPi) were high but triggering time was short, resulting in a large change in pleural pressure over a brief interval. At high levels of pressure support, dP/dt and PEEPi were low but triggering time was long, resulting in a smaller change in pleural pressure over a longer time. [Adapted, with permission, from Leung P, Jubran A and Tobin MJ. Comparison of assisted ventilator modes on triggering, patient effort, and dyspnea. Am J Respir Crit Care Med 155: 1940‐1948, 1997 .]



Figure 18.

Estimations of the duration of neural inspiratory time. Representative tracings of the raw crural diaphragmatic electromyogram (Edi), the processed Edi achieved by removing electrocardiography (EKG) artifacts by computer, the moving average (MA) of the processed Edi, esophageal pressure (Pes), and flow in a patient breathing spontaneously. The relationship between an indirect estimate of the onset of neural inspiratory time and its onset on the diaphragmatic EMG signal was assessed by calculation of the phase angle, expressed in degrees. In this example, the onset of inspiratory time is estimated as occurring earlier (negative phase angle of 15°) by esophageal pressure‐based measurements and later (positive phase angle of 110°) by flow‐based measurements. The duration of inspiratory time as estimated by esophageal pressure (hatched horizontal bar) is longer than the true inspiratory time measured by diaphragmatic electromyogram (note that the hatched bar is wider than 0‐360° on the solid black bar of the reference measurement). The duration of inspiratory time as estimated by flow‐based measurements is shorter (clear horizontal bar) than the true inspiratory time measured by diaphragmatic electromyogram (note that the open white bar is narrower than 0‐360° on the solid black bar of the reference measurement). [Adapted, with permission, from Parthasarathy S, Jubran A and Tobin MJ. Assessment of neural inspiratory time in ventilator‐supported patients. Am J Respir Crit Care Med 162: 546‐552, 2000 .]



Figure 19.

The phase angle between the indirect estimate of the onset of neural inspiratory time and its reference measurement in five patients during mechanical ventilation; estimates from the esophageal pressure (Pes) tracings are shown as closed squares, estimates from flow tracings are shown as closed circles, and estimates from transdiaphragmatic pressure (Pdi) tracings are shown as closed triangles. The closed symbols represent the mean difference (bias) in phase angle; the open symbols to the right of each closed symbol represent the mean difference between the two measurements noted during the reproducibility testing of the reference measurement. The error bars represent ±2 SD (twice the precision). A positive phase angle indicates a delay in the onset of neural inspiratory time for the flow‐based measurements. [Modified, with permission, from Parthasarathy S, Jubran A and Tobin MJ. Assessment of neural inspiratory time in ventilator‐supported patients. Am J Respir Crit Care Med 162: 546‐552, 2000 .]



Figure 20.

Failure to trigger the ventilator. Flow, airway pressure (Paw) and esophageal pressure (Pes) in a patient with COPD who is receiving assist‐control ventilation at the following settings: tidal volume 600 mL, inspiratory flow 60 L/min, trigger sensitivity −2 cmH2O and positive end‐expiratory pressure 0 cmH2O. The patient's intrinsic respiratory rate is 28 breaths/min, whereas the number of breaths delivered by the ventilator is 16 breaths/min. That is, 43% of the patient's inspiratory efforts fail to trigger ventilator assistance. Contractions of the inspiratory muscles during the failed triggering attempts cause a temporary deceleration of expiratory flow and much less obvious decreases in airway pressure. The temporary decelerations in expiratory flow are followed by temporary accelerations of expiratory flow that coincide with the termination of the unsuccessful inspiratory effort.



Figure 21.

The concordance between neural expiratory time and mechanical expiratory time can be quantified in terms of the phase angle, expressed in degrees. If neural activity begins simultaneously with the machine, the phase angle (θ) is zero. Neural activity beginning after the offset of mechanical inflation results in a positive phase angle (60° for Subject 1). Neural activity beginning before the onset of mechanical inflation results in a negative phase angle (−45° for Subject 2). [Adapted, with permission, from Parthasarathy S, Jubran A and Tobin MJ. Cycling of inspiratory and expiratory muscle groups with the ventilator in airflow limitation. Am J Respir Crit Care Med 158: 1471‐1478, 1998 .]



Figure 22.

Phase angle between neural and mechanical expiratory times before triggering (closed circles) and nontriggering (open circles) attempts. At pressure support (PS) of 10 and 20 cmH2O, the phase angle before nontriggering attempts exceeded that before triggering attempts, indicating that neural expiratory time during late mechanical inflation was longer before nontriggering attempts than before triggering attempts (for pressure support 10, P = 0.0002; for pressure support 20, P = 0.01). [Adapted, with permission, from Parthasarathy S, Jubran A and Tobin MJ. Cycling of inspiratory and expiratory muscle groups with the ventilator in airflow limitation. Am J Respir Crit Care Med 158: 1471‐1478, 1998 .]



Figure 23.

Four incidents of double triggering, each indicated by an arrowhead symbol (↑). Airway pressure (Paw) and esophageal pressure (Pes) in a patient with COPD and pneumonia who was receiving assist‐control ventilation at the following settings: tidal volume 600 mL, inspiratory flow 60 L/min, trigger sensitivity −2 cmH2O and positive end‐expiratory pressure 5 cmH2O. The duration of neural inhalation of the double‐triggered breaths, roughly equivalent to the width of the associated swings in esophageal pressure, was substantially longer than the neural inhalation of the normally triggered breaths.



Figure 24.

Volume stacking caused by double triggering. Flow (top panel), volume (middle panel), and esophageal pressure (lower panel) in a patient with COPD receiving assist‐control ventilation. During first breath, esophageal pressure remains positive indicating that the patient did not trigger the inflation. During the second breath, esophageal pressure becomes negative indicating active inspiratory effort, which lasts more than 1 s; the duration of mechanical inflation is 0.6 s. The longer duration of neural inspiration as compared with mechanical inflation causes the ventilator to deliver a second breath before there is time for exhalation. As a result, end‐inspiratory lung volume increases (breath stacking) with a consequent increase in elastic recoil. The increase in elastic recoil is responsible for the higher peak expiratory flow on the second breath as compared with the first breath.



Figure 25.

Influence of ventilator flow setting on patient effort. Flow (inspiration directed upward), airway pressure (Paw), and esophageal pressure (Pes) in a patient with respiratory failure who is receiving assist‐control ventilation; inspiratory flow is set at 60 L/min in the left panel and at 90 L/min in the right panel. At an inspiratory flow of 60 L/min (left panel), the pronounced negative deflection in airway pressure (patient effort to trigger the ventilator) together with subsequent extensive scalloping signifies that the inspiratory flow delivered by the ventilator is insufficient to meet the high demand. At an inspiratory flow of 90 L/min (right panel), the small negative deflection in airway pressure together with the subsequent smooth convex contour signifies that the delivered flow satisfies the patient's respiratory drive. Accordingly, the flow of 90 L/min achieved greater unloading of the respiratory muscles, as signaled by the shorter duration of inspiratory effort and the smaller swings in esophageal pressure.



Figure 26.

Continuous recordings of flow, esophageal pressure (Pes), and the sum of rib‐cage and abdominal motion in a patient with COPD receiving assist‐control ventilation at a constant tidal volume. As flow increased from 30 to 60 and 90 L/min (from right to left; i.e., the opposite of the usual presentation), frequency increased (from 18 to 23 and 26 breaths/min, respectively), PEEPi decreased (from 15.6 to 14.4 and 13.3 cmH2O, respectively), and end‐expiratory lung volume also fell. Increases in flow from 30 L/ min to 60 and 90 L/min also led to decreases in the swings in Pes from 21.5 to 19.5 and 16.8 cmH2O, respectively. [Adapted, with permission, from Laghi F, Segal J, Choe WK and Tobin MJ. Effect of imposed inflation time on respiratory frequency and hyperinflation in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 163: 1365‐1370, 2001 .]



Figure 27.

Changes in pressure‐time product (PTP) per minute (left panel), PTP per breath (middle panel), and frequency (right panel) as the level of intermittent mandatory ventilation (IMV) and pressure support (PS) were progressively increased in 11 ventilator‐dependent patients. Ventilator assistance of 0% represents unassisted breathing; PS of 100% represents the level necessary to achieve a tidal volume equivalent to that during assist‐control ventilation (10 mL/kg); IMV of 100% is the same ventilator rate as during assist‐control ventilation. The left panel shows that the rate of change in PTP per minute over the entire span of assistance did not differ between PS and IMV. The middle panel shows that the rate of change in PTP per breath decreased linearly as the rate of IMV was increased; the decrease with PS was linear only up a medium level and decreased little thereafter. The right panel shows that respiratory frequency decreased linearly as PS was increased, whereas it changed little with IMV until a high level of assistance was provided. See text for interpretation. [Based on data from Leung P, Jubran A and Tobin MJ. Comparison of assisted ventilator modes on triggering, patient effort, and dyspnea. Am J Respir Crit Care Med 155: 1940‐1948, 1997 .]



Figure 28.

Expiratory activity during mechanical inflation. Flow, airway pressure (Paw) and esophageal pressure (Pes) in a patient with COPD who is receiving assist‐control ventilation. The patient's first two inspiratory efforts (red vertical lines) trigger the ventilator successfully. The third and fourth inspiratory efforts are very weak (arrows) and do not trigger a mechanical inflation. The last inspiratory effort triggers the ventilator, and at the end of this mechanical inflation (blue vertical line) the patient recruits his expiratory muscles, producing an increase in esophageal pressure above the expected elastic recoil of the lung (dashed tracing) before the termination of mechanical inflation. Expiratory muscle recruitment produces a transient cessation of expiratory flow, which corresponds to a transient increase in esophageal pressure to approximately 20 cmH2O.



Figure 29.

Breath‐to‐breath values of tidal volume during 1 h of resting breathing in a patient with restrictive lung disease (top panel) and in a healthy control subject (bottom panel). The coefficient of variation for tidal volume in the patient (0.13) was more than five times smaller than that in the healthy subject (0.72). [Adapted, with permission, from Brack T, Jubran A and Tobin MJ. Dyspnea and decreased variability of breathing in patients with restrictive lung disease. Am J Respir Crit Care Med 165: 1260‐1264, 2002 .]



Figure 30.

Variability of breathing. Time series of airflow and esophageal pressure in a patient with acute respiratory failure secondary to an acute exacerbation of COPD who is being ventilated with pressure support of 5 cmH2O (PEEP, 0 cmH2O). The esophageal‐pressure tracing exhibits wandering values at end‐expiration and varying inspiratory excursions; these features are somewhat less evident on the flow tracing.



Figure 31.

The mean respiratory cycle during spontaneous breathing in seven weaning‐failure and ten weaning‐success patients. The early termination of inspiratory time in the weaning‐failure patients leads to a decrease in tidal volume. The decrease in inspiratory time, coupled with a decrease in expiratory time, results in a faster respiratory frequency. Bars represent 1 SE. [Adapted, with permission, from Tobin MJ, et al. The pattern of breathing during successful and unsuccessful trials of weaning from mechanical ventilation. Am Rev Respir Dis 134: 1111‐1118, 1986 .]



Figure 32.

A time‐series, breath‐by‐breath plot of respiratory frequency and tidal volume in a patient who failed a weaning trial. The arrow indicates the point of resuming spontaneous breathing. Rapid, shallow breathing developed almost immediately after discontinuation of the ventilator. [Adapted, with permission, from Tobin MJ, et al. The pattern of breathing during successful and unsuccessful trials of weaning from mechanical ventilation. Am Rev Respir Dis 134: 1111‐1118, 1986 .]



Figure 33.

The relationship between work of breathing and the frequency‐tidal volume (f/VT) ratio for a constant alveolar ventilation of 4 L/min based on the model of Otis and collaborators . Work of breathing is least for f/VT ratios of 37 to 59; it increases exponentially as f/VT increases from 59 to 234/min/L. [Adapted, with permission, from Tobin MJ, Laghi F and Brochard L. Role of the respiratory muscles in acute respiratory failure of COPD: lessons from weaning failure. J Appl Physiol 107: 962‐970, 2009 .]



Figure 34.

Two superimposed Campbell diagrams of work of breathing in a patient at the start and end of a trial of spontaneous breathing. Over the course of the weaning trial, the patient developed an increase in PaCO2 from 48 to 73 mmHg, but minimal change in overall work of breathing, suggesting that the hypoventilation resulted from either failure of respiratory motor output to increase during the weaning trial or an inability of the respiratory controller to sense the rise in PaCO2.



Figure 35.

Inspiratory resistance of the lung (Rinsp,L), dynamic lung elastance (Edyn,L), and intrinsic positive end‐expiratory pressure (PEEPi) in 17 weaning‐failure patients and 14 weaning‐success patients. Data displayed were obtained during the second and last minute of a T‐tube trial, and at one third and two‐thirds of the trial duration. Between the onset and end of the trial, the failure group developed increases in Rinsp,L (P < 0.009), Edyn,L (P < 0.0001), and PEEPi (P < 0.0001) and the success group developed increases in Edyn,L (P < 0.006) and PEEPi (P < 0.02). Over the course of the trial, the failure group had higher values of Rinsp,L (P < 0.003), Edyn,L (P < 0.006), and PEEPi (P < 0.009) than the success group [Adapted, with permission, from Jubran A and Tobin MJ. Pathophysiologic basis of acute respiratory distress in patients who fail a trial of weaning from mechanical ventilation. Am J Respir Crit Care Med 155: 906‐915, 1997 .]



Figure 36.

Respiratory effort during a weaning trial. Recordings of flow (inspiration directed upward) and esophageal pressure (Pes) in a patient with severe COPD who failed a weaning trial (left panel) and in a weaning‐success patient, who had been intubated because of an opiate overdose (and had no lung disease) (right panel), 10 min into a trial of spontaneous breathing. The weaning‐failure patient exhibits a steeper fall and greater excursion in esophageal pressure than did the weaning‐success patient—features that signify greater respiratory motor output. Despite the threefold larger excursion in esophageal pressure in the weaning‐failure patient, peak inspiratory flow in this patient is only twice as great as in the weaning‐success patient, signifying more abnormal mechanics in the weaning‐failure patient. The duration of respiratory cycle was shorter in weaning‐failure patient signifying tachypnea. The expiratory flow in the weaning‐failure patient demonstrates a supramaximal flow transient at the beginning of exhalation that is typical of expiratory flow limitation.



Figure 37.

Progressive increase in inspiratory effort in a weaning‐failure patient. Flow (top panel), esophageal pressure (Pes, middle panel), and airway pressure (Paw, lower panel) in a patient who developed severe respiratory distress while receiving continuous positive airway pressure (CPAP) of 5 cmH2O. The patient had developed respiratory failure (requiring mechanical ventilation) after developing a pulmonary embolus subsequent to undergoing lobectomy for lung cancer. The swings in esophageal pressure became progressively more negative over the first 30 s of the trial.



Figure 38.

Time‐series plot of swings in esophageal pressure (Pes; left panel) and frequency‐to‐tidal volume ratio (f/VT; right panel) during a trial of spontaneous breathing in a weaning‐failure patient. Black dots represent 1‐min averages. The solid line indicates the average value of Pes swings and f/VT of the final minute of the trial. The dashed lines indicate ±10% of the final minute values of Pes swings and f/VT. The time taken to reach ±10% of the final value was 14 min for Pes swings and 2 min for f/VT. [Adapted, with permission, from Jubran A, et al. Weaning prediction: esophageal pressure monitoring complements readiness testing. Am J Respir Crit Care Med 171: 1252‐1259, 2005 .]



Figure 39.

Esophageal pressure (Pes), gastric pressure (Pga), transdiaphragmatic pressure (Pdi), and compound motor action potential (CAMP) of the right and left hemidiaphragm after phrenic nerve stimulation before (left) and after (right) a T‐tube trial in a weaning failure patient. The end‐expiratory value of Pes and the amplitude of the right and left CAMPs were the same before and after the trial, indicating that the stimulations were delivered at the same lung volume and that the stimulations achieved the same extent of diaphragmatic recruitment. The amplitude of twitch Pdi elicited by phrenic nerve stimulation was the same before and after weaning. [Adapted, with permission, from Laghi F, et al. Is weaning failure caused by low‐frequency fatigue of the diaphragm? Am J Respir Crit Care Med 167: 120‐127, 2003 .]



Figure 40.

Interrelationship between the duration of a spontaneous breathing trial, tension‐time index of the diaphragm, and predicted time to task failure in nine patients who failed a trial of weaning from mechanical ventilation. The patients breathed spontaneously for an average of 44 min before a physician terminated the trial. At the start of the trial, the tension‐time index was 0.17, and the formula of Bellemare and Grassino (see text for details) predicted that patients could sustain spontaneous breathing for another 59 min before developing task failure. As the trial progressed, the tension‐time index increased and the predicted time to development of task failure decreased. At the end of the trial, the tension‐time index reached 0.26. That patients were predicted to sustain spontaneous breathing for another 13 min before developing task failure clarifies why patients did not develop a decrease in diaphragmatic twitch pressure. In other words, physicians interrupted the trial on the basis of clinical manifestations of respiratory distress, before patients had sufficient time to develop contractile fatigue. [Adapted, with permission, from Laghi F, Tobin MJ: Disorders of the respiratory muscles. Am J Respir Crit Care Med 2003; 168:10 .]



Figure 41.

Expiratory rise in gastric pressure (Pga) during the course of a weaning trial in failure () and success patients (). Between the onset and the end of the trial, increases in expiratory rise in Pga (P = 0.0005) occurred in failure patients but not in the success patients. Over the course of the trial, failure patients had higher values of expiratory rise in Pga (P = 0.004) than success patients. Bars represent ± SE. [Modified, with permission, from Parthasarathy S, Jubran A, Laghi F and Tobin MJ. Sternomastoid, rib‐cage and expiratory muscle activity during weaning failure. J Appl Physiol 103: 140‐147, 2007 .]



Figure 42.

Representative tracings of flow, Pes, and EMGscm in a weaning‐failure patient. Recordings were obtained during the first minute of the weaning trial, 40% of trial duration, and last minute of the trial. Phasic inspiratory activity of the sternomastoid muscle was evident within the first minute of the trial, and it increased progressively over the course of the trial. Note that phasic activity of the sternomastoids persists into expiration. [Adapted, with permission, from Parthasarathy S, Jubran A, Laghi F and Tobin MJ. Sternomastoid, rib‐cage and expiratory muscle activity during weaning failure. J Appl Physiol 103: 140‐147, 2007 .]



Figure 43.

Plots of tidal changes in esophageal pressure (ΔPes) against tidal changes in gastric pressure (ΔPga) in a weaning‐success patient and a weaning‐failure patient. At the start of a weaning trial, the success patient (top left panel) exhibited swings in esophageal pressure that became markedly more negative between the onset (closed symbol) and the end of inspiration (open symbol); in contrast, gastric pressure increased only slightly. Therefore, the slope of the PesPga plot at the onset of weaning (top left panel) was much greater than the slope recorded in healthy subjects during resting breathing, where the tidal change in gastric pressure is often greater than the tidal change in esophageal pressure. The steep PesPga plot (top left panel) indicates a greater‐than‐usual contribution of the rib‐cage muscles to tidal breathing than that of the diaphragm. Between the onset (top left panel) and the end of weaning (top right panel), the slope of the PesPga plot changed very little, indicating a constant contribution of the diaphragm and rib‐cage muscles to tidal breathing over the course of the weaning trial. In the case of the weaning‐failure patient, the inspiratory swings in esophageal pressure and gastric pressure had a similar pattern at the start of the trial to that in the success patient (bottom left panel). At the end of the trial, the failure patient exhibited a markedly negative slope in the PesPga plot, signifying a further increase in inspiratory rib‐cage muscle recruitment that was out of proportion to diaphragmatic recruitment.

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Martin J. Tobin, Franco Laghi, Amal Jubran. Ventilatory Failure, Ventilator Support, and Ventilator Weaning. Compr Physiol 2012, 2: 2871-2921. doi: 10.1002/cphy.c110030