Electronic Supplementary Material
Respiratory load compensation during mechanical ventilation
Proportional assist ventilation with load-adjustable gain factors vs. pressure support
Eumorfia Kondili, George Prinianakis, Christina Alexopoulou,
Eleftheria Vakouti, Maria Klimathianaki, and Dimitris Georgopoulos
Address for correspondence: Dimitris Georgopoulos, MD, PhD
Professor of Medicine,
Director of Intensive Care Medicine Department,
UniversityHospital of Heraklion,
Heraklion, Crete, 711 10,
Greece
e-mail:
Fax: +30-2810-392636
Methods
Ten patients admitted to the Intensive Care Unit for management of acute respiratory failure were studied. At the time of the study all patients were hemodynamically stable without vasoactive drugs and ventilated on pressure support mode through cuffed endotracheal (5 patients) or tracheostomy(5 patients) tubes. None of them was eligible for a weaning t-piece trial. The pressure support, positive end-expiratory pressure (PEEP) and fractional concentration of inspired O2 (FIO2) were determined by the primary physician, who was not involved in the study. In all patients PEEP was added to improve either the oxygenation or the triggering sensitivity. All patients were sedated with propofol (1.0-1.5mg/kg/h) to achieve acceptable oxygenation and patient-ventilator synchrony as judged by the primary physician. The level of sedation was such as to achieve a score of 3 on Ramsay's scale. Patients with one of the following characteristics were excluded: 1) pneumothorax with active chest tube leaks; 2) chest wall abnormalities (i.e., kyphoscoliosis); 3) overt pleural effusion; and 4) maximum inspiratory pressure >-20 cmH2O. The study was approved by the hospital ethics committee and informed consent was obtained from the patients or their families.
Measurements
Flow (V’) at the airway opening was measured with a heated pneumotachograph (Hans-Rudolf 3700, Kansas, USA) and a differential pressure transducer (Micro-Switch 140PC, Honeywell, Ontario, Canada), placed between the endotracheal tube and the Y-piece of the ventilator. Flow was electronically integrated to provide volume (V). Airway pressure (Paw; Micro-Switch 140PC, Honeywell, Ontario, Canada) was measured from a side port between the pneumotachograph and the endotracheal tube. Esophageal pressure (Pes) and gastric pressure (Pga) were measured (Micro-Switch 140PC, Honeywell, Ontario, Canada)with thin, latex balloon-tippedcatheter systems connected by polyethylene catheters to separatedifferential pressure transducers. The proper position of the balloons was verified using standard tests. Transdiaphragmatic pressure (Pdi) was derived by subtraction of Pes from Pga. Each signal was sampled at 150Hz (Windaq Instruments, Ohio, USA) and stored on a computer disk for later analysis.
Initially, the patients were connected to an ICU ventilator (Puritan-Bennett 840),able to ventilate them with PS and PAV. The ventilator was build up with a software program (PAV+) which, when PAV mode was activated,automatically estimated expiratory resistance (RrsPAV) and elastance (ErsPAV) of respiratory system, based on methods described previously[1, Section E2 of online supplement of re. 2)]. Briefly at random intervals of 4 to 10 breaths,a 300 msec pause maneuver at the end of selectedinspirations was applied and the Paw at end-inspiratory pause time (Pplat) was measured[1]. Assuming that Pplat was equal to end-inspiratory alveolar pressure (Palv),the ventilator software calculated ErsPAVas follows:
ErsPAV = (Pplat-PEEP)/VT, [Eq. 1]
where PEEP is positive end-expiratory airway pressure and VT is tidal volume. Obviously this method of elastance determination does not take into account the existence of intrinsic PEEP. Thus in the presence of dynamic hyperinflation ErsPAV overestimates the true elastance of respiratory system.
RrsPAV was measured during exhalation following a pause maneuver (see section E2 of the online supplement of ref. 2]. The software identified three points on the expiratory flow-time curve corresponding to peak flow and 5 msec and 10 msec. later. At these points Palv and total expiratory resistance (RTOT)were calculated as follows [Section E2 of the online supplement of ref. 2]:
Palv = Pplat – ΔVxErsPAV, [Eq. 2]
RTOT = (Palv – Paw)/V’ [Eq. 3]
where ΔV is the exhaled volume up to the point of interest and V’ and Paw are the corresponding expiratory flow and airway pressure, respectively. The values of RTOT at these points were averaged and an estimate of RTOT was obtained. RTOTis considered to be the sum of the flow-dependent resistance of the endotracheal tube (Rtube) and that of the respiratory system (RrsPAV). Rtube was calculated using the following equation:
Rtube = a + bV’, [Eq. 4]
where a and b were constants, depending on tube length and diameter, estimated using in vitro data. RrsPAV was derived by subtraction of Rtube from RTOT.
In an automated system in which interventions are applied randomly under unsupervisedconditions, safeguards need to be included to ensure that data obtained under unfavourable conditions are filtered out. Thus, all raw data were subjected to checks and theestimates of RrsPAVand ErsPAVwere discarded if any of the rejection pre-defined criteria were met [see reference 1 and 2 for details]. If ErsPAVwas rejected, RrsPAVwas also rejected.Valid estimates of RrsPAVand ErsPAVwere required for breath delivery,and were constantly updated by averaging new values withprevious values. This averaging process smoothes data and avoidsabrupt changes to breath delivery. If new values for RrsPAVand ErsPAVare rejected, the previous values remain active until valid newvalues are obtained. The ventilator software monitors the update processand generates an escalating alarm condition if the old values donot refresh.
With this system the caregiver sets the percentage of unloading (K) and the ventilator delivers pressure as follows:
Paw(t) = K [V’I(t) x (Rtube(t) + RrsPAV) + V(t) x ErsPAV] [Eq. 5]
Where Paw(t) is instantaneous airway pressure, V’I(t) is instantaneous inspiratory flow, V(t) is instantaneous lung volume above end-expiratory level and Rtube(t) is endotracheal tube resistance at V’I(t). Because the maximum value of K is limited to 95% of the measured values of elastance and resistance, the ventilator provides pressure which is always a fraction of the measured elastic and resistive pressure, avoiding thus the occurrence of runaway phenomena. These functional characteristics dictate that for a given inspiratory flow and volume, pressure assist decreases with decreasing RrsPAV and ErsPAV and increases with increasing RrsPAV and ErsPAV.
Study protocol
The patients were studied in semi-recumbent position (>45 degrees) in order to obtain as accurate a Pes signal as possible. Initially the patients were ventilated with pressure support at settings (pressure assist, PEEP and fractional concentration of inspired O2) determined by the primary physician and 30 min. later the pressure time product of the diaphragm per breath (PTPPdi/b) was calculated (see below). Thereafter the patients were placed on PAV+ and the percentage of unloading (K) was set at values which resulted in steady-state PTPPdi/b comparable to that obtained with PS. After determination of the percentage of unloading, at random order the patients were ventilated for 30 min.with PS and PAV+ with and without increase in the workload of respiratory system. The increase was obtained by applying sand bags on the entire surface of the anterior chest and abdominal wall. The sand bags were secured by strapping the chest and abdominal wall with non-elastic cloth corset with adjustable straps. The total applied weight and the straps wereadjusted such as to increase ErsPAVby at least 30%. If during the load application SaO2 decreased to <88% FIO2 was adjusted upward to obtain SaO2 >88%. At the end of each study period measurements of arterial blood gasses were obtained. In addition,the assist level wasdecreased to zero (CPAP only) for one breathto document the difference between assisted and non-assisted VT at the same chemical drive[3]. This procedure was repeatedfrom three to five times over a period of 1to 2min. and the values of unassisted VT were averaged.
At the end of the study, the patients were placed on volume-control constant flow mode and ventilated with VT comparable to that of assisted ventilation. The level of sedation was increased (propofol 6mg/kg/h plus fentanyl 2.5µg/kg/h) such as to achieve a score of 6 on Ramsay's scale. Simultaneously, breathing frequency was adjusted upward in order to lower PaCO2 and inhibit respiratory muscle activity. The absence of respiratory muscle activity was based on specific criteria[4]. In patients in whom respiratory muscle activity was not inhibited or the increase in respiratory rate was associated with increased PEEPi (higher than that observed during assisted mechanical ventilation), a neuromuscular blocking agent was administered (atracurium 25mg). Eight out of 10 patients needed a neuromuscular blocking agent. When passive ventilation was obtained the total respiratory system mechanics (resistance and elastance) were measured by the technique of rapid airway occlusion using standard formulas[5-7].. All the respiratory mechanics data were computed as an average of three measurements obtained by respective maneuvers satisfying passive condition. Respiratory system mechanics were obtained with and without load application.
Data analysis
The last two minutes of each 30 min period were analyzed and averaged to give the breath variables corresponding to each experimental condition. Pdi, Pes, Paw, V and V' were aligned at the beginning of neural inspiration, defined as the time that Pdi began to increase rapidly from the value reached during expiration. Pdi, Pga and Pes swings are reported as changes from end-expiratory value rather than from absolute zero pressure. This excludes the passive increase introduced by the application of the weight, permitting comparison of the active pressures generated under the different experimental conditions[8]. Neural inspiratory time (TIn) was measured as the interval between the beginning of Pdi increase and the point at which Pdi started to decline rapidly[9]. Neural expiratory time (TEn) was measured as the remainder of the respiratory cycle, determined from the Pdi waveform. The rate of rise of Pdi (dp/dt) wascalculated as the difference between peak Pdi and Pdi at the onset of neural inspiration divided by the corresponding time. The swings of Pdi(Pdiswings) during the respiratory cycle were measured as the difference between peak Pdi and Pdi at the onset of neural inspiration. Mechanical inflation (TIm) and deflation (TEm) times were measured as the intervals between the beginning and the end of inspiratory and expiratory flow, respectively. The level of PEEPi during the different experimental conditions was measured as the positive deflection of Pdi from the onset of neural inspiration to the point of zero flow[8, 10].
Inspiratory effort per breath was quantified by measuring the area under the Pdi signal from the beginning of Pdi increase to the point at which Pdi started to decline rapidly (PTPPdi/b). PTPdi/min was calculated as the product of the respective PTPdi per breath and breathing frequency. PTPPdi/L was calculated as PTPPdi/min divided by minute ventilation (V’E). PTPPdi/b was partitioned to that due to PEEPi (PTPPdiPEEPi/b, the area under the Pdi signal from the beginning of Pdi increase to the point of zero flow) and that due to inflation (the area under the Pdi signal from the point of zero flow to the point at which Pdi started to decline rapidly).
At 30%, 60% and 80% of inflation time the predicted Paw from Eq. 5 was calculated and compared with the corresponding values of observed Paw.
Data were analyzed by multi-factors analysis of variance for repeated measurements (ANOVA), followed by Tukey’s test for multiple comparison if the F-value was significant. Comparison between respiratory system mechanics measured during active and passive ventilation were made using the method of Bland ant Altman [11]. A p less than 0.05 was considered statistically significant. All values are expressed as mean ± SD.
Figures
Fig. S1: Upper panel: Relation between elastance of respiratory system estimated during proportional assist ventilation (ErsPAV) and elastance of respiratory system determined during controlled mechanical ventilation (ErsCMV) (P<0.001). Lower panel: Relation between expiratory total resistance (airway+endotracheal tube) estimated during proportional assist ventilation (RTOT) and minimum end-inspiratory resistance (airway+endotracheal tube) determined during controlled mechanical ventilation (Rmin) (P<0.001). Solid circles; without load. Open circles; with load. Dashed lines: lines of identity. Solid lines; regression lines.
Fig. S2: Bland-Altman analysis plot showing bias and agreement between elastance estimated during proportional assist ventilation (ErsPAV) and during controlled mechanical ventilation (ErsCMV). Inner dashed line: mean difference.Outer dashed lines: 95% confidence limits (±1.96 SD) of the difference between methods. Solid circles; without load. Open circles; with load.
Fig. S3: Bland-Altman analysis plot showing bias and agreement between resistancesestimated during proportional assist ventilation (RTOT) and during controlled mechanical ventilation (Rmin). Inner dashed line: mean difference.Outer dashed lines: 95% confidence limits (±1.96 SD) of the difference between methods. Solid circles; without load. Open circles; with load.
Fig. S4: Individual (closed circles connected with solid lines) and mean (open circles connected with dashed lines) load-induced increases in diaphragmatic pressure-time product per breath (ΔPTPPdi/b, cmH2O.s), per minute (ΔPTPPdi/min, cmH2O.s/min) and per liter of ventilation (ΔPTPPdi/L,cmH2O.s /l), transdiaphragmatic swings (ΔPdiswings, cmH2O), inspiratory drive (Δdp/dt, cmH2O/sec) and neuroventilatory coupling (ΔVT/PTPPdi/b, l/cmH2O.s).
*Significantly different from the corresponding value with PAV+
Table S1: Individual data of respiratory system mechanics with load off
Pt. no.PEEPiPAVPEEPiPSErsPAVErsCMVRTOTRmin Rmax
10.30.42521101113
20.30.12537101117
31.21.22225141620
40.40.53835161931
52.32.52427161321
60.00.03342131217
70.60.8193881015
80.30.912710710
91.31.7231114715
101.20.53028241822
ErsCMV (cmH2O/l), Rmax, Rmin (cmH2Ol/sec): passive end-inspiratory elastance, maximum end-inspiratoty resistance, minimum (airway) end-inspiratory resistance, respectively, measured during volume control ventilation (passive ventilation). ErsPAV (cmH2O/l) RTOT (cmH2O/l/sec): respiratory system elastance and total airway resistance, respectively, measured during PAV+ (active respiratory efforts). PEEPiPAV (cmH2O): intrinsic PEEP with PAV+. PEEPiPS (cmH2O): intrinsic PEEP with PS.
Table S2: Individual data of respiratory system mechanics with load on
Pt. no.PEEPiPAVPEEPiPSErsPAVErsCMVRTOTRmin Rmax
10.30.43424151215
21.00.93343131214
31.82.12929151823
45.84.05557162530
54.04.53744251924
62.01.9676113817
73.14.44846121419
80.71.0171512610
99.79.03216152024
103.26.44239342629
See table S1 for abbreviations.
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