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Anesth Analg 2008; 106:1491-1494
© 2008 International Anesthesia Research Society
doi: 10.1213/ane.0b013e318168b4cd
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TECHNOLOGY, COMPUTING, AND SIMULATION

The Impact of Different Step Changes of Inspiratory Fraction of Oxygen on Functional Residual Capacity Measurements Using the Oxygen Washout Technique in Ventilated Patients

Hermann Heinze, MD, Beate Sedemund-Adib, MD, Matthias Heringlake, MD, Ulrich W. Gosch, MD, Hartmut Gehring, MD, and Wolfgang Eichler, MD

From the Department of Anaesthesiology, University of Luebeck, Luebeck, Germany.

Address correspondence and reprint requests to Dr. Hermann Heinze, Department of Anaesthesiology, University of Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany. Address e-mail to Hermannheinze{at}ngi.de.


   Abstract
Top
 Abstract
Introduction
 METHODS
 RESULTS
 DISCUSSION
 CLINICAL CONSIDERATIONS
 REFERENCES
 
BACKGROUND: Functional residual capacity (FRC) measurements may help to guide respiratory therapy. Using the oxygen washout technique, FRC can be assessed at bedside during spontaneous breathing. High repeatability, crucial for monitoring, has not been shown in ventilated patients. A large step change of inspiratory fraction of oxygen (Fio2) ({Delta}Fio2) may impede the clinical use in patients ventilated with high Fio2. We investigated the repeatability of FRC measurements and the impact of different {Delta}Fio2 on this repeatability.

METHODS: The LUFU system (Draeger Medical, Luebeck, Germany) estimates FRC by oxygen washout, a variant of multiple-breath-nitrogen-washout during a fast {Delta}Fio2. In 20 postoperative cardiac surgery patients, FRC was measured in duplicate using {Delta}Fio2 of 0.1, 0.2, and 0.6.

RESULTS: There were no differences between repeated measurements of FRC, neither using a {Delta}Fio2 of 0.1, 0.2 nor 0.6({Delta}0.1: 2.62 L ± 0.58, 2.62 L ± 0.59, P = 0.995; {Delta}0.2: 2.70 L ± 0.59, 2.66 L ± 0.56, P = 0.258; {Delta}0.6: 2.61 L ± 0.58, 2.59 L ± 0.58, P = 0,639). Coefficients of variation were 6.6%, 5.6%, and 6.6%, respectively.

CONCLUSIONS: FRC can be measured in ventilated patients using the oxygen washout technique with a clinically acceptable repeatability. Repeatability is not significantly influenced whether using a {Delta}Fio2 of 0.1, 0.2, or 0.6.


   Introduction
Top
 Abstract
 Introduction
METHODS
 RESULTS
 DISCUSSION
 CLINICAL CONSIDERATIONS
 REFERENCES
 
Measurement of functional residual capacity (FRC) has been advocated for monitoring and optimizing respiratory therapy in patients with acute lung injury (ALI) or adult respiratory distress syndrome (ARDS).1–3 Because of the lack of easily applicable bedside monitoring devices, indirect methods, such as the static pressure-volume curve and the upper and lower inflection point or the alveolar pressure volume curve, have been used to guide ventilatory strategy.4 Other methods used to assess FRC, such as computed tomography,5 positron emission tomography,6 rebreathing in a closed circuit, or by multiple breath washout techniques using sulfur-hexafluoride,7or nitrogen,8,9 are not practical for clinical use. Recently, acceptable accuracy of a FRC monitoring device (LUFU, Draeger Medical, Luebeck, Germany) was demonstrated using the oxygen washout technique in spontaneously breathing healthy volunteers and patients.10–12 Absolute values of FRC are of less interest than their trend or change after, e.g., a recruitment maneuver, whereas good repeatability is important for comparing measurements.

A large step change of the inspiratory fraction of oxygen ({Delta}Fio2) of e.g., 0.6 for oxygen washin and washout (wi/wo) used in our previous study12 could severely affect oxygenation in patients with ALI or ARDS ventilated with high Fio2, and therefore may impede the clinical use of the device. The manufacturer states that a {Delta}Fio2 of at least 0.1 will yield sufficiently accurate FRC measurements, but the success of this approach has not been demonstrated in ventilated patients.

The purpose of our study was therefore to investigate the repeatability of duplicate measurements in ventilated patients using the oxygen washout technique and the effect of different step changes in Fio2 on repeatability.


   METHODS
Top
 Abstract
 Introduction
 METHODS
RESULTS
 DISCUSSION
 CLINICAL CONSIDERATIONS
 REFERENCES
 
After approval by the local ethics committee and written informed patient consent, we studied 20 cardiac surgery patients without preexisting lung diseases for 6 h after surgery. Patients with unstable hemodynamics, i.e., adrenaline >0.05 µg · kg–1 · min–1, dobutamine >5 µg · kg–1 · min–1, or milrinone >0.3 µg · kg–1 · min–1 were excluded, as well as patients ventilated with positive end-expiratory pressure (PEEP) >10 mbar or Fio2 >0.4. All patients were transported to the intensive care unit for postoperative therapy after uncomplicated cardiac surgery with cardiopulmonary bypass in mild hypothermia. All patients were mechanically ventilated with biphasic positive airway pressure ventilation (Evita XL, Draeger Medical). Patients were sedated with continuous infusion of propofol and intermittent boluses of piritramid or pethidine (Ramsay score 3-4). No muscle relaxing drugs were administered. Before start of the study protocol, a standardized recruitment maneuver was applied to the patients’ lungs (PEEP 15 mbar, positive inspiratory pressure 35-40 mbar for 30 s) and the patients were allowed to stabilize hemodynamically for 10 min. Airway pressures were adjusted to deliver a tidal volume of 6-8 mL/kg predicted body weight. Patients’ lungs were ventilated with a Fio2 of 0.4; PEEP was set according to the ARDS Network trial PEEP/Fio2 tables.13 Respiratory rate was adjusted to achieve normocapnia.

FRC Measurement
The LUFU system (Draeger Medical) estimates FRC by oxygen washout, a variant of multiple breath nitrogen washout. The exact technical and mathematical description has been published.14 Briefly, a sidestream O2-analyzer calculates FRC from the end-inspired- and end-expired concentrations of O2 during a step change of the inspired O2-concentration. Measurement is started by increasing the Fio2 by at least 0.1 [wash-in (wi)]. FRC measurement is terminated automatically when the accumulated net ventilated volume is larger than eight times the calculated FRC. After termination of measurement, Fio2 is decreased back to baseline Fio2 [washout (wo)]. We calculated the mean FRC after one wi and the consecutive wo.

Sequence of Measurement
In randomized order, using the sealed envelope technique, FRC was measured in each patient with {Delta}Fio2 of 0.1, 0.2, and 0.6 by increasing Fio2 from 0.4 to 0.5, 0.6, and 1.0 and back to 0.4 ({Delta}Fio2_1). Measurement was repeated with each {Delta}Fio2 ({Delta}Fio2_2) resulting in a total of six individual FRC values for each patient (Fig. 1).


Figure 127
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  		Figure 1. Sequence of measurement. Functional residual capacity (FRC) measurements (mean of one washin and washout) in 20 postoperative ventilated cardiac surgery patients obtained in randomized order with different step changes of inspired fraction of oxygen ({Delta}Fio2). With each {Delta}Fio2, i.e., {Delta}0.1, {Delta}0.2, and {Delta}0.6 FRC was measured in duplicate.

 

Statistics
From the data of a study by Olegard et al.,15 a power analysis was performed. We calculated that 20 patients were needed with {alpha} = 0.05 and β = 0.80, to detect a maximal difference between duplicate measurements of 50 mL, a difference we considered clinically relevant. Data are presented as mean ± sd. Measurements with the same {Delta}Fio2 were compared using the t-test for repeated measurements. As this test is intended to find differences and not similarities between repeated measures, the effect size d was calculated. A value of d < 0.2 indicates a very low chance the values being different.16 The coefficient of variation (CV) was calculated as the sd of the differences divided by the mean of all measurements.17


   RESULTS
Top
 Abstract
 Introduction
 METHODS
 RESULTS
DISCUSSION
 CLINICAL CONSIDERATIONS
 REFERENCES
 
The demographic data of the 20 patients studied are summarized in Table 1. There were no differences between repeated measurements of FRC, neither using a {Delta}Fio2 of 0.1, 0.2, nor 0.6 for oxygen wi/wo. Effect size d was below 0.2 for each {Delta}Fio2. The differences between consecutive measurements using the same {Delta}Fio2 ranged from 0% to 1.5% with a CV from 5.6% to 6.6% (Table 2).


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  		Table 1. Demographic Data

 

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  		Table 2. Statistical Data for Duplicate Functional Residual Capacity Measurements in 20 Postoperative Cardiac Surgery Patients

 


   DISCUSSION
Top
 Abstract
 Introduction
 METHODS
 RESULTS
 DISCUSSION
CLINICAL CONSIDERATIONS
 REFERENCES
 
This study shows clinically acceptable repeatability of duplicate FRC measurements in mechanically ventilated patients using the oxygen washout technique. This repeatability is in the same range as comparable methods of FRC measurement tested in lung models, as well as in ventilated patients.8,9,15,18,19 In addition, there was no significant difference in repeatability whether using a {Delta}Fio2 of 0.1, 0.2, or 0.6 for oxygen wi/wo.

Zinserling et al. and Wrigge et al. showed repeatability coefficients of 6.0% in ventilated patients8 and 13% during partial ventilatory support9 using the multibreath nitrogen washout method. With a modified nitrogen washin/washout technique requiring a small {Delta}Fio2, Olegard et al. showed a bias of duplicate measurements of –5 mL with a 95%-confidence interval [–38 mL; 29 mL].15 Recently, di Marco et al. described a method of helium dilution during partial support ventilation for FRC measurement and reported a CV of 3.2%.19 The CV of measurements using the oxygen washout technique presented here is well in the recommended range of 5%-8%.17 Maisch et al.10 demonstrated less precision of duplicate measurements with the LUFU system in spontaneous breathing. One reason may be that although the LUFU system accounts for inspiratory and expiratory changes of lung volume,14 which are common during spontaneous breathing with variations in breathing pattern, this may increase measurement errors as much as 10%, especially if tidal volume is <400 mL.14 This should be considered when using FRC measurements during the weaning period. Further studies should address this issue. Another reason may be that Maisch et al. compared one wi with the consecutive wo. Because of the diffusion of tissue nitrogen resulting in a measurement error of about 5% during a single washin or single washout procedure, Olegard et al. proposed that a normal FRC measurement is found in a combined wi/wo of oxygen.15 Our study reinforced this observation, as repeatability was higher when using the mean of one wi and one wo (data not shown).

Besides the technical problems when using a high {Delta}Fio2 for wi/wo, i.e., a great change of viscosity of the sample gas, thereby introducing a significant change of sample delay,8,14 this may impede the clinical use in patients requiring high Fio2 to maintain adequate arterial oxygenation. As repeatability did not differ significantly while using different {Delta}Fio2, FRC measurements may be possible in this patient group by using a small {Delta}Fio2 of 0.1 or 0.2.

One important limitation of our study is that we assumed that FRC does not change between repeated measurements. But the bilevel positive airway pressure (BIPAP) ventilation mode we used is likely to result in variation of tidal volume, which may contribute to variations of FRC. In addition, spontaneous breathing during BIPAP may lead to recruitment of previously collapsed alveoli. This could influence the repeatability, even in measurements following one after the other within minutes. Surely, the use of a volume-controlled ventilation mode together with the use of muscle relaxing drugs would have provided better experimental study conditions, but we decided to use the BIPAP mode and allowed spontaneous breathing for the following reasons: First, as we were interested in the feasibility of FRC measurements in routine clinical practice, we decided to use the standard ventilation mode used in our institution. Repeatability may be higher when using a volume-controlled ventilation mode and muscle relaxants, but this information is not very important for routine clinical practice. Assisted ventilation allowing the patient to breath spontaneously has gained more interest and, in addition, BIPAP ventilation is increasingly used during intensive care treatment or postoperative ventilation.20,21

Second, the use of muscle relaxation has been implicated in postoperative pulmonary complications by reducing FRC and increasing the risk for silent aspiration after tracheal extubation, and routine administration is therefore not recommended.22

Another important limitation of this study is the patient population, as we specifically excluded patients with significant pulmonary pathology. Although postcardiac surgery patients exhibit some degree of lung injury, overall lung injury scores in our patients were low. Patients with more pulmonary dysfunction such as those with ALI or ARDS or obstructive pulmonary diseases may profit most from serial FRC measurements. We cannot say if repeatability is in the same range in these patients. Before routine FRC measurements can be recommended, the repeatability of the oxygen washout method in such patients remains to be demonstrated.

As we only randomized the sequence of duplicate measurements using the same {Delta}Fio2, we cannot directly compare measurements with different {Delta}Fio2. As each wi and wo maneuver lasts at least 4-6 min, the total duration of measurements lasted at least 60 min (Fig. 1). There are not much data on postoperative variations of FRC, but even without a recruitment maneuver between measurements the mechanical ventilation with PEEP in the range of 5-8 mbar may have recruited lung tissue, leading to an increased FRC. On the other hand resorption atelectasis as the result of ventilation with a Fio2 of 1.0 may have decreased FRC during that period,23 both would have influenced repeatability. Therefore, we did not directly compare measurements using different {Delta}Fio2.


   CLINICAL CONSIDERATIONS
Top
 Abstract
 Introduction
 METHODS
 RESULTS
 DISCUSSION
 CLINICAL CONSIDERATIONS
REFERENCES
 
FRC measurements have been advocated to guide respiratory therapy. But as no individual "optimal" FRC is known, increased FRC values, e.g., after a recruitment maneuver or a higher PEEP level, may also be due to hyperinflation. FRC monitoring may be of more value for indicating derecruitment, e.g., after accidental disconnection of the respirator or endotracheal suctioning. A decreased FRC may indicate a potential for alveolar recruitment.

Many studies have shown that bedside assessment of FRC during mechanical ventilation, partial ventilatory support, or spontaneous breathing is possible with acceptable accuracy and repeatability,8–10,12,15,19 but there are fewer studies showing clinical benefit for the patients. Erlandsson et al. optimized PEEP using FRC measurements in conjunction with electrical impedance tomography during bariatric surgery.24 Future investigation should evaluate if a FRC-guided therapy may improve a patient’s condition.

We conclude that our data demonstrate (1) a clinically acceptable repeatability of FRC measurements in mechanically ventilated patients with relatively normal pulmonary function and (2) no influence on repeatability whether using a {Delta}Fio2 of 0.1, 0.2, or 0.6 for oxygen wi and wo. More data are needed to verify the technique in patients with ALI/ARDS, as these patients may profit most from bedside FRC measurements.


   ACKNOWLEDGMENTS
 
This study was supported by institutional resources of the Department of Anesthesiology, University of Luebeck, Germany. The authors thank Dräger Medical, Luebeck, Germany for providing the LUFU system and Dr. Dieter Weismann for his technical support.


   Footnotes
 
Accepted for publication January 8, 2007.


   REFERENCES
Top
 Abstract
 Introduction
 METHODS
 RESULTS
 DISCUSSION
 CLINICAL CONSIDERATIONS
 REFERENCES
 

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