1Department of Anesthesiology and Intensive Care, University Hospital, Uppsala, Sweden and Zentralklinikum Augsburg, Germany. 2Department of Anesthesiology and Critical Care Medicine, University of Freiburg, Freiburg, Germany. 3Department of Anesthesiology and Intensive Care, University Hospital, Uppsala, Sweden. 4Department of Plastic Surgery, University Hospital, Uppsala, Sweden. 5Department of Anesthesiology and Intensive Care and Dept of Otorhinolaryngology University Hospital, Uppsala, Sweden
Accepted for publication: May 25, 2000
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Abstract |
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Br J Anaesth 2000; 85: 57786
Keywords: complications, acute respiratory failure; ventilation, positive end-expiratory pressure
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Introduction |
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We studied surfactant-deficient piglets, and obtained information for setting PEEP and VT both from the static PV-curve and from the slice-compliance technique. We compared settings of PEEP and VT derived from static mechanics with those derived from the slice-compliance curve, in terms of the mechanical stress imposed to the respiratory system (end-inspiratory plateau pressure (Pplat) and the shape of the volume-dependent compliance curve), and gas exchange (arterial PO2).
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Materials and methods |
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Anaesthesia and fluid management
Lavage
Lavage was performed as previously described13 14 with 11 broncho-alveolar lavages (1.21.5 litres normal saline, corresponding to 5060 ml kg1) which we have found causes a PaO2/FIO2 of <20 kPa. Between each lavage, the animals were ventilated for 5 min with pressure-controlled ventilation, FIO2 1.0, PEEP 15 cm H2O and VT 15 ml kg1. The effects of lavage on gas exchange, respiratory mechanics, and extravascular lung water (double-indicator dilution15 16) were compared between volume-controlled ventilation at ZEEP during healthy conditions and the surfactant-deficient conditions immediately after lavage. After lavage the animals were allowed to stabilize for 20 min.
Study design
After lavage, all animals underwent volume-controlled ventilation with the ventilator set according to both static (STAT) and dynamic (DYN) measurements, each setting being applied for 40 min (see Fig. 1). To compensate for time-related effects and to use the individual animals as their own controls, the animals were allocated randomly to settings by either method first. The effects of STAT and the DYN settings were also compared with the healthy conditions before lavage, with PEEP set to 4 cm H2O (PEEP 4).
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Static measurements for ventilator adjustment
Static mechanics were used to determine the LIP and the UIP for setting PEEP (at the level of LIP) and VT (below UIP).
The lower inflection point of the static PV curve of the respiratory system was determined by a modified multi-occlusion technique17 as follows: a recruitment manoeuvre (see below) was performed to standardize the PV-history of the lung. Ventilation was started at zero PEEP, frequency of 16 min1, I:E 1:1 and with constant inspiratory flow. Seven breaths with a VT of 50 ml each were applied. At the end of the last breath, an end-inspiratory hold of 5 s was performed and the end-inspiratory airway pressure (Pplat) noted. For the next step, VT was increased to 100 ml at otherwise identical settings. The procedure was repeated with VT increased in steps of 50 ml up to 600 ml (corresponding to 24 ml kg1). The resulting values of plateau pressures after a 5 s end-inspiratory hold were used to construct the inflation limb of a static PV-loop (PV-curve) from which LIP and UIP were determined by tracing a straight line on the linear part as the best fit by eye.
Dynamic measurements for ventilation adjustment
Dynamic measurements were made to adjust the DYN settings and also to estimate indirectly the mechanical stress on the respiratory system after 40 min of ventilation at DYN and at STAT settings.
To detect non-linearities in dynamic respiratory system compliance within the tidal volume range, the slice method was used12 18 which measures volume-dependent dynamic compliance and resistance breath by breath. The method continuously calculates tracheal pressure (Ptrach)19 by subtracting the flow-dependent resistive pressure drop caused by the resistance of the endotracheal tube (ETT) from the pressure measured at the airway opening. The resulting Ptrach VT loop is divided into consecutive volume slices and mean compliance (intrinsic PEEP considered) and mean resistance (ETT resistance excluded) is calculated for each slice by repeated application of the linear resistance-compliance model (RC-model). To reduce the effect of cardiac oscillations, the slice values of 20 consecutive breaths were averaged and used for the analysis (see Fig. 3; for the sake of clarity, the SD for each slice-compliance value is omitted in Figs 2 and 5). Combining the compliance and resistance values of all the slices gives the course of compliance and resistance within VT (i.e. the volume-dependent compliance and resistance within one breath). The interpretation of the slice-compliance over VT plots was as follows: the compliance curve represents the slope, i.e. the first derivative of the S-shaped PV-curve. The derivative of an S-shaped curve results in a trapeziform curve.7 The lower bow of the S-curve is the ascending part and the upper bow is the descending part of the trapeziform compliance curve. The steepest middle segment of the S-curve is the horizontal and highest part of the compliance curve, which was the target of our DYN settings. The advantage of considering the derivative (compliance) curve rather than the original (PV) curve is that compliance, as a differential value, is very sensitive to changes in the shape of the PV-curve. A horizontal course of the dynamic slice-compliance within a single tidal volume suggests that a constant volume change per pressure change be obtained. If an ascending shape was present, PEEP was increased to see whether this resulted in a greater initial compliance level and a longer horizontal course of the compliance over the VT. If a descending shape was found, an inappropriately high PEEP and/or VT was assumed and adjustments were made (see below) to obtain a horizontal slice-compliance curve at a high absolute compliance level.
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Ventilator settings
Ventilatory frequency was 25 min1, FIO2 0.3, inspiration-to-expiration ratio 1:1 and inspiratory flow constant during all study modes.
Both mechanics as well as PaCO2 were taken into account for setting PEEP and VT:
For the STAT settings, PEEP was set to the level of LIP, and VT initially at 10 ml kg1. During the subsequent 40 min, blood gases were checked every 10 min and VT was adjusted with respect to PaCO2, while PEEP was adjusted with respect to the two point compliance of the respiratory system (Crs, 2P). If PaCO2 was above 6.5 kPa, VT was increased in steps of 1 ml kg1 until PaCO2 5.56.5 kPa. With PaCO2 <5.5 kPa, VT was reduced in steps of 1 ml kg1. Airway pressures were also measured every 10 min and Crs, 2P was determined. If Crs, 2P decreased to 90% or less of its initial level where PEEP=LIP, reduction of PEEP in steps of 2 cm H2O was considered.
For the DYN settings, PEEP was initially set at 12 cm H2O and VT at 10 ml kg1, which we have found gives adequate gas exchange in most animals. During the subsequent 40 min, blood gases were checked and dynamic mechanics were analysed every 10 min, and PEEP and VT were adjusted for an approximately horizontal shape of the slice-compliance curve. If an ascending shape of the slice-compliance appeared, PEEP was increased in steps of 2 cm H2O. If a descending shape appeared, PEEP was reduced in steps of 2 cm H2O. VT was adjusted to keep the PaCO2 within 5.56.5 kPa and increased or decreased in steps of 1 ml kg1. (A representative example of the approach is given in Fig. 3.)
Respiratory mechanics determined at PEEP and VT after ventilator settings made using static/dynamic measurements
The end-inspiratory plateau pressure (Pplat) for both the STAT and the DYN settings was determined by performing an end-inspiratory hold for 5 s using the inspiratory hold function of the ventilator. The hold was performed with the VT and the PEEP level applied that had been set according to static or dynamic mechanics.
Two point compliance of the respiratory system (Crs, 2P) was calculated according to the formula: Tidal volume/(end-inspiratory pressure end-expiratory pressure). To measure the end-expiratory pressure, the expiratory hold function of the ventilator was used for 5 s. Crs, 2P was determined with the VT and the PEEP level applied that had been set according to static or dynamic mechanics, respectively. Intrinsic PEEP was considered when expiratory flow had not decreased to zero at end-expiration.
Re-expansion
The lungs were re-expanded immediately after lavage, as well as before STAT and DYN by a 5-min period of pressure-controlled ventilation with a frequency of 20 min1, I:E 1:1, FIO2 0.3, PEEP 25 and a peak inspiratory airway pressure of 50 cm H2O. The re-expansion effect immediately after lavage was assessed in terms of Crs, 2P setting the ventilator for 2 min to the pre-lavage PEEP 4 settings.
Monitoring
Intravascular catheters were surgically placed to measure central venous, pulmonary artery (via the external jugular vein), and aortic pressures (via the carotid artery). The position of the catheters was confirmed by pressure tracing. Cardiac output was determined from arterial thermodilution curves21 (Pulsion Medical Systems, Munich, Germany). Unlike measurements of right heart flow with thermodilution in the pulmonary artery, arterial thermodilution is influenced minimally by ventilation-induced intrathoracic pressure changes. The anaesthetised-paralysed animals were studied in the physiological prone position. At the end of the experiment, the animals were killed with potassium chloride.
Anesthesia and fluid management
Anaesthesia was induced with an injection of tiletamine 3 mg kg1; zolazepam 3 mg kg1; xylazine 2.2 mg kg1; atropine 0.04 mg kg1 intramuscularly and deepened with ketamine 100 mg, and morphine 1 mg kg1 i.v. Anaesthesia was maintained with infusions of ketamine (20 mg kg1 h1) and morphine (0.5 mg kg1 h1), and muscle relaxation obtained by continuous infusion of pancuronium bromide (0.25 mg kg1 h1). The animals were given a solution of 4.5 g litre1 NaCl with 25 g litre1 glucose (Rehydrex, Pharmacia Infusion AB, Uppsala, Sweden) at 10 ml kg1 h1 and a bolus of dextran-70 10 ml kg1 (Macrodex 70, Pharmacia Infusion AB) to ensure normovolaemia.
Data presentation and statistics
Data are presented as mean (SD) or mean (95% confidence interval). Differences were evaluated with a non-parametric analysis of variance (Friedman test). Significant differences were evaluated using the paired sign test with correction for multiple comparisons,22 and significance was accepted with P0.05. Where appropriate, the exact P value is also indicated.
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Results |
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An UIP immediately after lavage did not appear in all PV-curves. If present, it was 32 (2836) cm H2O (see Fig. 4 for the individual PV-curves). This corresponded to a rapidly descending shape of the slice-compliance curve. This shape was also quite often seen despite Pplat<UIP.
In all animals after 40 min of ventilation using STAT settings, the slice compliance curve showed a rapid decrease whereas it was nearly horizontal after 40 min of ventilation at DYN settings with only a slight tendency to decrease (see Fig. 5). Under no condition was intrinsic PEEP observed nor tube obstruction detected.
Cardiac index was greater with DYN (164 (132196) during STAT, and 202 (169235) ml min kg1 during DYN, P<0.01), (see Fig. 6) as was oxygen delivery (14 (1217) compared with 17 (1420) ml min kg1, P0.01).
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Discussion |
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Critique of methods
The slice-compliance
There is increasing evidence that it is difficult, if not impossible, to infer the behaviour of lung units from the mechanical behaviour measured at the airway opening, i.e. from the PV-relation.410 Why then do we measure respiratory system mechanics? One obvious motive is to indirectly estimate and reduce the mechanical stress to the respiratory system with appropriate ventilator settings. The PV-relation reflects the sum of all mechanical events occurring within the respiratory system and being transferred to the airway opening. Events at specific structures or regions of the lung will not be evident from this sum signal.9 If the forces producing different mechanical events at different locations oppose each other, the resultant sum signal is difficult to analyse without far reaching assumptions about the relative contribution of those forces. Whether, for example, a particular volume is accommodated in the central airways, the terminal airways or the alveoli, and which of those structures are distended or overdistended by that volume cannot be derived from the PV-relation. However, some conclusions regarding the respiratory system as a whole can be drawn from the PV-relation. (1) A steep PV-relation (= high compliance) shows that insufflating the volume increment under study requires a relatively small pressure increment. No matter how the insufflated volume is distributed to the different lung structures, those lung structures that are filled will be subjected to a lower mechanical stress when compliance is great compared with a smaller compliance condition. (2) Since the PV-relation (and, consequently, the compliance) may be non-linear over the tidal volume, the mechanical stress imposed to the respiratory system will be reduced if the entire VT can be applied at a constant high compliance. (3) A decreasing compliance during the tidal volume inflation indicates increasing mechanical stress to the affected structure(s). (4) An increasing compliance could reflect different intrapulmonary events like, for example, opening of lung units during inspiration6 or decreasing pressure requirements with increasing volume following the Laplace law or changes in the visco-elastic properties.23 As a simple test, PEEP is increased: if this results in a higher compliance which is constant over a greater part of the VT, the mechanical conditions of the respiratory system have probably improved (no matter what particular changes at what particular structures have brought about the improvement).
The slice-compliance does not include a model of the visco-elastic properties of the respiratory system. Generally speaking, visco-elastic properties can only be determined by changing from dynamic conditions to static ones. Such conditions are obtained with an end-inspiratory occlusion manoeuvre where the energy stored in visco-elastic elements during actual inspiration is released and can be estimated by the slow pressure decrease to the plateau pressure (although not unequivocally, since different time constants can also affect this pressure change). Visco-elasticity has been expressed as a spring-and-dashpot model.23 Because the slice-compliance procedure does not model visco-elasticity, a small bias in favour of the STAT-settings may have been introduced since LIP is estimated during static conditions and, hence, without any visco-elastic pressure components.
Slice-compliance uses a linear RC-model successively applied to different volume slices, so that the linear RC-model is restricted to 1/8 of the volume range of the VT. Using the linear RC-model repeatedly and separately for each of the consecutive slices preserves the robustness of the least-squares fit algorithm and analyses non-linearity, with the only assumption that this non-linearity can be divided into several consecutive, small and linear segments.
Limitations of the study
The determination of LIP by visual inspection (see Fig. 4) is inaccurate. Harris and colleagues have shown24 that inter-observer variability determining inflection points visually can be considerable with a maximum difference of 11 cm H2O for the same patient. An objective method for determining LIP would have strengthened our study.
With respect to the adjustment of PEEP one might ask whether these adjustments were fully comparable between dynamic and static settings. The LIP was determined before the study settings. Since the PV-manoeuvre is itself a kind of recruitment,7 10 determining LIP repeatedly was not considered. Adjustments of PEEP during STAT settings would have been necessary if Crs,2P (determined every 10 min) had changed. When VT was reduced to adjust for PaCO2, Crs,2P increased slightly (5%; data not given). A decrease in Crs,2P, however, was never observed during the 40-min period with static settings. Therefore we did not test the assumption that this would have indicated overdistension and required a PEEP reduction. We might have found that increasing VT (obtaining lower Crs,2P) and decreasing PEEP in order to maintain Crs,2P, as foreseen in the study protocol, might have produced end-expiratory collapse, and this would have revealed that, in retrospect, the protocol in this particular point was not based on a sound physiological rationale. Instead, PEEP, once set at the level of LIP, did not have to be changed during the STAT settings, nor was there ever any need to increase VT to obtain normocapnia. The determination of LIP was not repeated since the PV-manoeuvre is stressful. A potential change in lung mechanics during the 40-min period of application could, therefore, have gone unnoticed.
The current study did not include oesophageal pressure data. In patients, LIP can be affected by chest wall mechanics.25 26 We cannot exclude the possibility that the high LIP was also influenced by chest wall mechanics.
Finally, the number of animals was too small to definitely exclude any difference in PaO2 between STAT and DYN, and we acknowledge that with more animals the tendency of PaO2 to decrease with DYN settings could be a relevant difference between both settings. (To detect a true difference in PaO2 of 2 kPa with 0.70 power and a SD of 3 kPa for PaO2, 28 animals would have been necessary.)
Titrating PEEP during actual ventilation
It was not surprising that the (indirect) indicators of mechanical stress at end-inspiration (Crs,2P and Pplat) were less with the lower PEEP during DYN settings (see Fig. 6). Neither Crs,2P nor Pplat, however, reflect non-linearities of compliance during the course of inspiration. The assumptions for using LIP as a guide to optimal PEEP are (1) that inspiratory compliance during actual ventilation is as linear as is the compliance above LIP for the static circumstance, and (2) that this linear segment of the static PV-curve indicates complete alveolar recruitment. The latter assumption has been challenged.4 5 710 As regards the assumption of a linear compliance during the inspiratory phase of the actual ventilation, our data suggest that using the static PV-curve for setting PEEP (and VT) results in pronounced non-linearities of the compliance, and the decreasing shape of the compliance curve indirectly suggests that inspiratory mechanical stress was higher with the STAT settings (see Fig. 5). In contrast, after 40 min of ventilation at DYN settings the slice compliance was greater and had a more horizontal shape (see Fig. 5). Adjustments of ventilator settings based on slice-compliance analysis are possible during uninterrupted ventilation, which is an advantage compared with the static approach which needs an artificial manoeuvre for constructing the PV-curve. Although clinical extrapolation is premature, these data challenge the uncritical use of the static PV-loop for making ventilator settings. Studies in which PEEP was set according to LIP and to a rather high level3 found reduced mortality, but whether this was due to an open lung condition, i.e. to a reduction of mechanical stress during the entire ventilatory cycle, or to other PEEP effects, as yet unclear, has not been shown. The static conditions are so different from those of actual ventilation that it is hard to imagine how and why the former should apply to the latter. The difference between PEEP according to the LIP level and PEEP according to slice-compliance most likely reflects the different PV-history of the respiratory system during static compared to dynamic conditions.
Assessment of full alveolar recruitment
Our case is based on evidence for full alveolar recruitment, which can only be estimated indirectly. Different indicators for alveolar recruitment have been used,2729 and in the current study, in addition to Crs,2P upon re-expansion immediately after lavage, PaO2 was used despite evidence for a weak association of oxygenation and respiratory mechanics.30 With oxygenation and Crs,2P at (or near) its healthy level, full alveolar recruitment is likely. In our lavage-model, rigorous recruitment manoeuvres precede the ventilatory patterns under study and full alveolar recruitment is probably thereby achieved.
The PaO2 reduction of 3 kPa during dynamic settings compared with static settings was inconclusive (P=0.07 for the PaO2 difference STAT vs DYN, see Fig. 6 and Table 1). The small number of animals precludes definite conclusions. We assume, however, that functioning lung units were not de-recruited with the lower PEEP during DYN. First, lowering airway pressures during DYN increased cardiac output (see Fig. 6) which, as described by Dantzker and co-workers,31 might increase shunt and, hence, reduce PaO2. However, no major increase in venous admixture was observed (see Table 1). Also, we have found that in the porcine lavage model critically low PaO2 values rapidly develop once the airway pressure is below the threshold to keep the lung open. If the PEEP-reduction during DYN had induced local alveolar closure, we would have expected rapid progress to major collapse with life-threatening hypoxaemia. For this reason we considered a 40-min period sufficient for assessing short-term effects of different ventilator settings. The beneficial short-term circulatory effects of the DYN setting were not unexpected. Those effects have certainly a very limited impact on barotrauma / volutrauma, which is the clinically more relevant outcome variable but can only be studied in long-term experiments.
Titrating VT
The study protocol also included adjustments of VT (see Fig. 3) according to mechanical and blood gas criteria, but we never had to increase VT. (Strictly speaking, changes in volume at constant frequency and inspiratory time always imply changes in inspiratory flow, too, but the potential effect of each of these effects could not be evaluated separately.) The UIP derived from static mechanics indicated overdistension at higher pressure levels than dynamic mechanics did: during STAT settings, Pplat (35 cm H2O) was clearly above the UIP of about 32 cm H2O, and this corresponded to a rapidly descending part of the slice-compliance plot. However, even when Pplat was below UIP, we frequently found a descending slice-compliance curve, indicating overdistension, which would not have been inferred from consideration of the UIP.
We conclude that in the atelectasis-prone porcine surfactant-deficient model, non-invasive analysis of volume-dependent dynamic compliance showed that, for keeping the lung open during ventilation, PEEP could be set 5 cm H2O lower than LIP. With pulmonary gas exchange maintained at an appropriate level, this gave a greater two-point compliance of the respiratory system (Crs,2P), smaller end-inspiratory plateau pressure (Pplat), and greater slice-compliance with a more horizontal course, all indirectly suggesting less mechanical stress to the respiratory system.
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Acknowledgements |
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Footnotes |
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References |
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