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(Chest. 2003;123:2050-2056.)
© 2003 American College of Chest Physicians

Dead Space Ventilation in Critically Ill Children With Lung Injury*

Jorge A. Coss-Bu, MD; David L. Walding, BSBE; Yadin B. David, PhD and Larry S. Jefferson, MD

* From the Section of Critical Care Medicine, Department of Pediatrics, Baylor College of Medicine, Houston, TX.

Correspondence to: Jorge A. Coss-Bu, MD, Critical Care Section, Texas Children’s Hospital, 6621 Fannin St, Suite 440, MC 2-3450, Houston, TX 77030-2399; e-mail: jorgec{at}bcm.tmc.edu


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Study objective: In children with acute lung injury, there is an increase in minute ventilation (E) and inefficient gas exchange due to a high level of physiologic dead space ventilation (VD/VT). Mechanical ventilation with positive end-expiratory pressure, when used in critically ill patients to correct hypoxemia, may contribute to increased VD/VT. The purpose of this study was to measure metabolic parameters and VD/VT in critically ill children.

Design: A cross-sectional study.

Setting: Pediatric ICU of a university hospital.

Patients: A total of 45 mechanically intubated children (mean age, 5.5 years).

Interventions: Indirect calorimetry was used to measure metabolic parameters. VD/VT parameters were calculated using the modified Bohr-Enghoff equation. ARDS was defined based on criteria by The American-European Consensus Conference.

Measurements and results: The group mean (± SD) ventilatory equivalent for oxygen (VeqO2) and ventilatory equivalent for carbon dioxide (VeqCO2) were 2.9 ± 1 and 3.3 ± 1 L per 100 mL, respectively. The group mean VD/VT was 0.48 ± 0.2. When compared to non-ARDS patients (33 patients), the patients with ARDS (12 patients) had a significantly higher VeqO2 (3.3 ± 1 vs 2.8 ± 1 L per 100 mL, respectively; p < 0.05), a significantly higher VeqCO2 (3.7 ± 1 L/100 vs 3.1 ± 1 L per 100 mL, respectively; p < 0.05), and a significantly higher VD/VT (0.62 ± 0.14 vs 0.43 ± 0.15, respectively; p < 0.0005).

Conclusions: Critically ill children with ARDS have increased VD/VT. Increased VD/VT was the main cause of the excess of E demand in these patients. Increased metabolic demands, as shown by the VeqO2, VeqCO2, and ventilatory support, are the major determinants of E requirements in children with ARDS.

Key Words: acute lung injury • critical care • indirect calorimetry • mechanical ventilation • pediatrics • respiratory dead space


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Since the initial description of the ARDS by Ashbaugh et al,1 mechanical ventilation with positive end-expiratory pressure (PEEP) has been used in critically ill patients with lung injury to correct the hypoxemia and the loss of lung volume commonly seen in this population.2 3 4 5 An increase in minute ventilation (E) also has been reported in critically ill patients who are receiving mechanical ventilation,6 with this demand of E being determined by the following three factors: carbon dioxide output (CO2); PaCO2; and the efficiency of CO2 removal.7

Any increase in dead space will cause a decrease in the efficiency of CO2 removal and a consequent increase in the E requirements out of proportion to the level of metabolic demand for gas exchange. The use of mechanical ventilation contributes to this increased physiologic dead space ventilation (VD/VT),8 9 10 11 12 as does inefficient gas exchange due to alterations in the distribution of the ventilation-perfusion relationship and a high level of VD/VT.13 14 15 16 17 Increased dead space has been reported14 15 18 19 20 21 in patients early on in the clinical course of ARDS and is thought to be associated with the presence of primary lung injury.

Studies in critically ill and mechanically ventilated adults have reported simultaneous measurements of metabolic parameters and VD/VT.6 22 23 Dead space measurements with simultaneous measurements of metabolic parameters also have been reported in critically ill and mechanically ventilated neonates,24 25 26 anesthetized infants and children undergoing cardiac surgery,27 28 29 30 31 32 and critically ill children.33

The purpose of this study was to measure metabolic and VD/VT parameters in critically ill children receiving ventilatory support and to assess the effect of lung injury on VD/VT in this population.


   Materials and Methods
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 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
This cross-sectional study measured metabolic and VD/VT parameters in 45 critically ill children who had been admitted to a pediatric ICU. The protocol was approved by the institutional review board for studies involving human subjects, and informed parental consent was obtained before the study.

While receiving mechanical ventilation, a previously validated mass spectrometer for children was used to measure metabolic parameters by using a breath-by-breath technique of indirect calorimetry.34 Indirect calorimetry is a bedside technique that allows the accurate measurement of energy expenditure (EE). It involves the analysis of expired gas for oxygen and carbon dioxide levels and for the measurement of expired volume. When indirect calorimetry measurements by a metabolic cart are combined with arterial blood gas analysis for carbon dioxide, the VD/VT can be determined individually.

Demographic data were collected including the following: age; sex; and day-of-study data for weight, pediatric risk of mortality (PRISM) score, therapeutic intervention scoring system (TISS) score, length of stay in the pediatric ICU, and length of mechanical ventilation. Time-of-study data obtained from the ventilator settings included the following: fraction of inspired oxygen (FIO2); PEEP; tidal volume (VT); E; synchronized intermittent mandatory ventilation (SIMV); peak inspiratory pressure (PIP); and mean airway pressure (Paw). The oxygenation index (ie, Paw x FIO2 x 100/PO2 in the blood) and the ventilation index (ie, PCO2 in the blood x PIP x SIMV/100) were calculated.

The metabolic parameters included the following: oxygen consumption (O2); CO2; VeqO2 (E/O2), VeqCO2 (E/CO2); and mixed expired carbon dioxide (PeCO2). The clinical protocol for the measurements have been described previously.35

At the same time as the metabolic evaluation, an arterial blood sample was obtained for PaCO2, and the modified Bohr-Enghoff equation36 (ie, PaCO2 - PeCO2/PaCO2) was used to calculate VD/VT. Spearman correlation was utilized to analyze the relationship between mechanical ventilation and VD/VT. The {Delta}PCO2was calculated. In order to assess differences in the calculation of the VD/VT, we used the following three different methods: (1) VD/VT I = the Bohr-Enghof equation; (2) VD/VT II = (end-tidal carbon dioxide - PeCO2)/end-tidal carbon dioxide; and (3) VD/VT III = [1 - (CO2)/PaCO2 x E)]. The Bland-Altman analysis was used to estimate bias and variability between the methods.37 Utilizing the definition by Tulla et al,38 increased VD/VT was defined as a value of > 0.40.

To evaluate the participation of PaCO2, VD/VT, and CO2 in the amount of ventilatory support expressed as E, each of these factors was assumed to have a normal value while the other two had the real values obtained for each patient. Therefore, three different values of E were obtained (ie, E I, E II, and E III). E was calculated using the following formula: E = 0.863 x CO2 calculated/[PaCO2 x (1 - VD/VT)], with each correspondent value being substituted into the previous equation. E I was defined as a PaCO2 value of 40 mm Hg, E II was defined as a VD/VT value of 0.40, and E III was defined as a calculated value of CO2, where CO2 calculated is the normal CO2 from EE based on values from Talbot,39 and where EE = 5.68 x O2 + 1.59 x CO2. The calculated values for E I, E II, and E III then were compared against the measured values.

To analyze the effect of lung injury on VD/VT parameters, the patients were divided in two groups (ARDS and non-ARDS) based on the criteria of the American-European Consensus Conference on ARDS.40 The t test was used to compare data between groups. The Spearman correlation was calculated when appropriate. All values are given as the mean ± SD.


   Results
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 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Forty-five patients (20 female patients and 25 male patients) participated in the study. The mean age of the patients was 5.5 ± 5.4 years (range, 0.25 to 18 years), and the mean weight was 19 ± 14 kg (range, 4 to 55 kg). The patient’s clinical diagnoses included the following: sepsis (10 patients); bacterial pneumonia (14 patients); viral pneumonia (6 patients); postoperative (8 patients); malignancies (5 patients); and Stevens-Johnson syndrome (2 patients). The mean length of stay in the ICU at the time of the study was 21 ± 25 days, with a mean time receiving mechanical ventilation of 15 ± 14 days. The mean PRISM score on the day of the study was 11 ± 5 points, and the mean TISS score on the day of the study was 27 ± 8 points.

The mean ventilator parameters were as follows: FIO2, 0.50 ± 0.10; PEEP, 6 ± 2 cm H2O; VT, 11 ± 4 mL/kg; E, 5.1 ± 2.9 L/min; SIMV, 18 ± 8 breaths/min; PIP, 46 ± 15 cm H2O; and Paw, 11 ± 5 cm H2O. The mean oxygenation index was 7 ± 6, and the mean ventilation index was 48 ± 42.

The group average metabolic measurements values showed a O2 of 10 ± 5 mL/kg/min, a CO2 of 9 ± 4 mL/kg/min, a VeqO2 of 2.9 ± 1 L per 100 mL, a VeqCO2 of 3.3 ± 1 L per 100 mL, and a PeCO2 of 24 ± 6 mm Hg. The dead space measurements showed an average VD/VT of 0.48 ± 0.2. The relationship between VD/VT and ventilatory parameters showed a correlation value for SIMV of 0.53 (p < 0.0005), for PEEP of 0.43 (p < 0.005), for VT of -0.08 (p = 0.59), and for VE of -0.20 (p = 0.17). The mean PaCO2 was 51 ± 18 mm Hg, and the mean {Delta}PCO2 was 5 ± 10 mm Hg. The average values of E I, E II, and E III were 5.7 ± 3, 4.3 ± 3, and 3.5 ± 3 L/min, respectively.

The average bias between VD/VT I and VD/VT II was 0.04 (p < 0.005, different from zero), with a variability of 0.09 (Fig 1 ). The average bias between VD/VT I and VD/VT III was -0.02 (p < 0.005, different from zero), with a variability of 0.04 (Fig 1) .



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  		Figure 1. Top: the average of VD/VT I and VD/VT II vs the difference between the two methods. The solid horizontal line is the estimated bias, and the dashed horizontal lines are the variability (± 2 SDs). Bottom: the average of VD/VT I and VD/VT III vs the difference between the two methods. The solid horizontal line is the estimated bias, and the dashed horizontal lines are the variability (± 2 SDs).

 
The use of the criteria of the American-European Consensus Conference on ARDS resulted in 12 patients meeting the criteria of ARDS, and a total of 33 patients not meeting the criteria for ARDS (Table 1 ). In addition, the patients with ARDS had a significantly higher VD/VT (0.62 ± 0.14 vs 0.43 ± 0.15, respectively; p < 0.0005) [Fig 2 ]. Patients with the criteria for ARDS had a significantly higher VeqO2 (3.3 ± 1 vs 2.8 ± 1 L per 100 mL, respectively; p < 0.05), a higher VeqCO2 (3.7 ± 1 vs 3.1 ± 1 L per 100 mL, respectively; p < 0.05), and a higher {Delta}PCO2 (16 ± 12 vs 1 ± 6 mm Hg, respectively; p < 0.0001) compared to patients without the criteria for ARDS. All the methods of calculating E demonstrated a significant difference between patients with and without ARDS, for E I (52 ± 55% vs 9 ± 26%, respectively; p < 0.005), for E II (40 ± 22% vs 8 ± 24%, respectively; p < 0.0005), and for E III (7 ± 29% vs 35 ± 22%, respectively; p < 0.005).


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  		Table 1. Comparison Between Patients With ARDS and Non-ARDS Patients*

 


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  		Figure 2. Bar chart of VD/VT expressed as a fraction. Hatched bars represent ARDS patients, and open bars represent non-ARDS patients. Values are given as the mean ± 95% confidence interval.

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
The purpose of this study was to measure the metabolic and VD/VT parameters in critically ill children and to assess the effect of lung injury on VD/VT in children on mechanical ventilation.

Several studies6 10 13 have reported VD/VT results in mechanically ventilated preoperative adult patients, with values ranging from 0.31 to 0.36. The values reported in pediatric preoperative patients have ranged from 0.35 to 0.38.27 29 30 It has been described that patients with ARDS, sepsis, and trauma require increased ventilatory support to meet the higher ventilatory needs associated with a hypermetabolic state. This increased need for ventilatory support is associated with a concomitant change in VD/VT. A recent study by Nuckton et al41 found that increased dead space fraction as a consequence of pulmonary vascular injury42 43 was observed in adults patients with ARDS and was associated with an increased risk of death.

Several clinical studies6 13 16 41 have measured VD/VT in critically ill adult patients with ARDS with VD/VT values ranging from 0.46 to 0.69. The studies24 25 26 performed in newborn patients reported VD/VT values ranging from 0.47 to 0.62. A report by Lum et al33 measured VD/VT parameters in 12 critically ill children who were receiving mechanical ventilation (mean age, 5.6 years), and the mean VD/VT value was 0.38. The present study of 45 critically ill children who were receiving mechanical ventilation showed a mean VD/VT value of 0.48. This result was not significantly different when compared to the values reported in the above-mentioned studies that were conducted in newborn and adult patients (Table 2 ).


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  		Table 2. Comparison of VD/VT Measurements*

 
In addition, a total of 28 patients, representing 62% of the total sample we evaluated, had increased VD/VT, which was defined as a value of > 0.40. This was similar to previous values reported in adult patients,6 22 newborn patients,25 26 and pediatric patients.27 44 Also, 92% of all the patients with ARDS in our study showed an increase in physiologic dead space, with an average value of 0.62. This possibly was a consequence of increased ventilatory support, as evidenced by a significantly higher mean Paw, in this group.

In a prospective study by Nuckton et al,41 the authors measured the dead space fraction in 179 adult patients who were receiving ventilatory support and had a diagnosis of ARDS, and the results showed a significantly higher mean dead space fraction among the patients who died compared to the survivors (0.63 vs 0.54, respectively). These values are similar to the results seen in our study. The findings of the study by Nuckton et al,41 indicate that a substantial increase in alveolar dead space occurs very early in the course of the ARDS, reflecting the extent of pulmonary vascular injury.

The relationship of ventilatory support and VD/VT in the present study showed a significant correlation of SIMV, PEEP, and Paw with VD/VT, without a significant correlation with VT or E. The mechanisms that explain the changes in dead space, in relation to respiratory frequency, are based on the observation that a slower frequency allows for more even ventilation and for emptying of all alveolar units, particularly units with a prolonged time constant. This is similar to the described higher VD/VT per minute in infants, as related to a faster resting respiratory frequency.30

The use of PEEP as a method to increase Paw in critically ill patients is a common intervention that is used to improve oxygenation and to restore a low functional residual capacity. With the use of higher distending pressures, some lung areas will be overdistended, resulting in fewer alveolar units participating in gas exchange and an increase in dead space. In this study, we did not find a significant relationship between VD/VT and VT, but a significant correlation was noted between physiologic dead space (volume) and VT. Several studies have reported a significant correlation between physiologic dead space and VT in anesthetized dogs,45 in anesthetized patients,46 and in critically ill patients with ARDS.17 The increase in VT will result in a proportional increase in alveolar ventilation, but this change in alveolar ventilation is attenuated by a concomitant change in physiologic dead space.

The use of different formulas to calculate dead space has been described in the literature. The initial description of calculating the dead space based on the measurement of exhaled gas was published in 1891 by Bohr.47 In 1938, Enghoff48 modified the original equation by substituting the value of PACO2 by the use of PaCO2. Several studies using the original Bohr equation have reported VD/VT results in preoperative patients.10 23 30 Some reports have documented the significance of using the modified Bohr-Enghoff equation in order to accurately calculate VD/VT parameters, particularly in patients with lung disease16 and pulmonary hypoperfusion.27 29 In these patients, the difference between PACO2 and PaCO2 increases with decreasing pulmonary blood flow and a increased amount of intrapulmonary shunting. In our study, the {Delta}PCO2 was significantly higher in patients with ARDS, with an average value of 16 mm Hg, compared to an average value of 1 mm Hg in patients without the criteria for ARDS. The result of using PACO2 values in the patients having either lung disease or decreased pulmonary flow will result in an underestimation of physiologic dead space and an overestimation of alveolar dead space.

The present study reports the results of comparing three different formulas used to calculate VD/VT by using the Bland-Altman analysis. The results showed significant bias and large variability when comparing the Bohr-Enghoff equation against the other two formulas. In critically ill pediatric patients, it appears that the use of PACO2 will carry a significant error in the calculation of VD/VT.

The use of the VeqO2 has been described22 as a parameter with which to assess the ability of the lung to extract oxygen. A large value suggests that the patient is unable to support metabolic demands without ventilatory assistance.22 In this study, the VeqO2 in ARDS patients was significantly higher compared to that in non-ARDS patients, implying that an elevated E is needed to compensate for the inability of the injured lung to extract oxygen and deliver it to the tissues. The VeqCO2 is the ventilatory indication of the degree of inefficiency in the pulmonary removal of carbon dioxide. Patients with ARDS had a significantly higher value compared to non-ARDS patients as a consequence of the lung becoming less efficient in removing carbon dioxide.

It is known that the level of carbon dioxide and increased VD/VT are important factors in the ventilatory needs of critically ill patients. The level of carbon dioxide and the VD/VT had major impacts on E needs in patients with ARDS, accounting for changes of 52% and 40%, respectively, in the measured E, assuming normal values for each of these two parameters. The influence of carbon dioxide production was not significant in the amount needed for E, probably because the patients with ARDS had a lower measured value, reducing the participation of this parameter in the calculation of E.

In summary, in critically ill children the major determinants of E and VD/VT are significant lung injury and increased metabolic demands. The use of PaCO2 is important in the accurate calculation of dead space in patients with significant lung injury.


   Footnotes
 
Abbreviations: EE = energy expenditure; FIO2 = fraction of inspired oxygen; Paw = airway pressure; PeCO2 = mixed expired carbon dioxide; PEEP = positive end-expiratory pressure; PIP = peak inspiratory pressure; PRISM = pediatric risk of mortality; SIMV = synchronized intermittent mandatory ventilation; TISS = therapeutic intervention scoring system; CO2 = carbon dioxide output; VD/VT = physiologic dead space ventilation; E = minute ventilation; VeqCO2 = ventilatory equivalent for carbon dioxide; VeqO2 = ventilatory equivalent for oxygen; O2 = oxygen consumption; VT = tidal volume

This research was supported by the National Institutes of Health General Clinical Research Center and by the Genevieve R. McClelland Fund for Pediatric Intensive Care Research.

Received for publication March 21, 2002. Accepted for publication October 29, 2002.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Ashbaugh, DG, Bigelow, DB, Petty, TL, et al (1967) Acute respiratory distress in adults. Lancet 2,319-323[ISI][Medline]
  2. Luce, JM, Robertson, HT, Huang, T, et al The effects of expiratory positive airway pressure on the resolution of oleic acid-induced lung injury in dogs. Am Rev Respir Dis 1982;125,716-722[ISI][Medline]
  3. Pepe, PE, Hudson, LD, Carrico, CJ Early application of positive end-expiratory pressure in patients at risk for the adult respiratory-distress syndrome. N Engl J Med 1984;311,281-286[Abstract]
  4. Pelosi, P, Cereda, M, Foti, G, et al Alterations of lung and chest wall mechanics in patients with acute lung injury: effects of positive end-expiratory pressure. Am J Respir Crit Care Med 1995;152,531-537[Abstract]
  5. Weisman, IM, Rinaldo, JE, Rogers, RM Current concepts: positive end-expiratory pressure in adult respiratory failure. N Engl J Med 1982;307,1381-1384[ISI][Medline]
  6. Kiiski, R, Takala, J Hypermetabolism and efficiency of CO2 removal in acute respiratory failure. Chest 1994;105,1198-1203[Abstract/Free Full Text]
  7. Milic-Emili, J, Aubier, M Some recent advances in the study of the control of breathing in patients with chronic obstructive lung disease. Anesth Analg 1980;59,865-873[Free Full Text]
  8. Crossman, PF, Bushnell, LS, Hedley-Whyte, J Dead space during artificial ventilation: gas compression and mechanical dead space. J Appl Physiol 1970;28,94-97[Free Full Text]
  9. Fletcher, R Deadspace during anaesthesia. Acta Anaesthesiol Scand Suppl 1990;94,46-50[Medline]
  10. Puri, GD, Venkataraman, RK, Singh, H, et al Physiological dead space and arterial to end-tidal CO2 difference under controlled normocapnic ventilation in young anaesthetised subjects. Indian J Med Res 1991;94,41-46[ISI][Medline]
  11. Suwa, K, Bendixen, HH Change in PaCO2 with mechanical dead space during artificial ventilation. J Appl Physiol 1968;24,556-562[Free Full Text]
  12. Stockwell, MA, Bruce, W, Soni, N The influence of CO2 production and physiological deadspace on end-tidal CO2 during controlled ventilation: a study using a mechanical model. Anaesth Intensive Care 1989;17,482-486[ISI][Medline]
  13. Kiiski, R, Takala, J, Kari, A, et al Effect of tidal volume on gas exchange and oxygen transport in the adult respiratory distress syndrome. Am Rev Respir Dis 1992;146,1131-1135[ISI][Medline]
  14. Dantzker, DR, Brook, CJ, Dehart, P, et al Ventilation-perfusion distributions in the adult respiratory distress syndrome. Am Rev Respir Dis 1979;120,1039-1052[ISI][Medline]
  15. Ralph, DD, Robertson, HT, Weaver, LJ, et al Distribution of ventilation and perfusion during positive end-expiratory pressure in the adult respiratory distress syndrome. Am Rev Respir Dis 1985;131,54-60[ISI][Medline]
  16. Shimada, Y, Yoshiya, I, Tanaka, K, et al Evaluation of the progress and prognosis of adult respiratory distress syndrome: simple respiratory physiologic measurement. Chest 1979;76,180-186[Abstract]
  17. Kiiski, R, Kaitainen, S, Karppi, R, et al Physiological effects of reduced tidal volume at constant minute ventilation and inspiratory flow rate in acute respiratory distress syndrome. Intensive Care Med 1996;22,192-198[CrossRef][ISI][Medline]
  18. Greene, R, Zapol, WM, Snider, MT, et al Early bedside detection of pulmonary vascular occlusion during acute respiratory failure. Am Rev Respir Dis 1981;124,593-601[ISI][Medline]
  19. Bachofen, M, Weibel, ER Alterations of the gas exchange apparatus in adult respiratory insufficiency associated with septicemia. Am Rev Respir Dis 1977;116,589-615[ISI][Medline]
  20. Tomashefski, JF, Jr, Davies, P, Boggis, C, et al The pulmonary vascular lesions of the adult respiratory distress syndrome. Am J Pathol 1983;112,112-126[Abstract]
  21. Idell, S, Mazar, AP, Bitterman, P, et al Fibrin turnover in lung inflammation and neoplasia. Am J Respir Crit Care Med 2001;163,578-584[Free Full Text]
  22. Kinney, JM, Askanazi, J, Gump, FE, et al Use of the ventilatory equivalent to separate hypermetabolism from increased dead space ventilation in the injured or septic patient. J Trauma 1980;20,111-119[ISI][Medline]
  23. Kiiski, R, Takala, J, Eissa, NT Measurement of alveolar ventilation and changes in deadspace by indirect calorimetry during mechanical ventilation: a laboratory and clinical validation. Crit Care Med 1991;19,1303-1309[ISI][Medline]
  24. Arnold, JH, Thompson, JE, Benjamin, PK Respiratory deadspace measurements in neonates during extracorporeal membrane oxygenation. Crit Care Med 1993;21,1895-1900[ISI][Medline]
  25. Arnold, JH, Bower, LK, Thompson, JE Respiratory deadspace measurements in neonates with congenital diaphragmatic hernia. Crit Care Med 1995;23,371-375[CrossRef][ISI][Medline]
  26. Wenzel, U, Wauer, RR, Schmalisch, G Comparison of different methods for dead space measurements in ventilated newborns using CO2-volume plot. Intensive Care Med 1999;25,705-713[CrossRef][ISI][Medline]
  27. Burrows, FA Physiologic dead space, venous admixture, and the arterial to end-tidal carbon dioxide difference in infants and children undergoing cardiac surgery. Anesthesiology 1989;70,219-225[CrossRef][ISI][Medline]
  28. Fletcher, R Invasive and noninvasive measurement of the respiratory deadspace in anesthetized children with cardiac disease. Anesth Analg 1988;67,442-447[Abstract/Free Full Text]
  29. Lindahl, SG, Yates, AP, Hatch, DJ Relationship between invasive and noninvasive measurements of gas exchange in anesthetized infants and children. Anesthesiology 1987;66,168-175[CrossRef][ISI][Medline]
  30. Hulse, MG, Lindahl, SG, Hatch, DJ Comparison of ventilation and gas exchange in anaesthetized infants and children during spontaneous and artificial ventilation. Br J Anaesth 1984;56,131-135[Abstract/Free Full Text]
  31. Fletcher, R, Niklason, L, Drefeldt, B Gas exchange during controlled ventilation in children with normal and abnormal pulmonary circulation: a study using the single breath test for carbon dioxide. Anesth Analg 1986;65,645-652[Abstract/Free Full Text]
  32. Fletcher, R Gas exchange during thoracotomy in children: a study using the single-breath test for CO2. Acta Anaesthesiol Scand 1987;31,391-396[ISI][Medline]
  33. Lum, L, Saville, A, Venkataraman, ST Accuracy of physiologic deadspace measurement in intubated pediatric patients using a metabolic monitor: comparison with the Douglas bag method. Crit Care Med 1998;26,760-764[CrossRef][ISI][Medline]
  34. Coss-Bu, JA, Jefferson, LS, Walding, D, et al Resting energy expenditure in children in a pediatric intensive care unit: comparison of Harris-Benedict and Talbot predictions with indirect calorimetry values. Am J Clin Nutr 1998;67,74-80[Abstract]
  35. Coss-Bu, JA, Jefferson, LS, Walding, D, et al Resting energy expenditure and nitrogen balance in critically ill pediatric patients on mechanical ventilation. Nutrition 1998;14,649-652[CrossRef][ISI][Medline]
  36. Fletcher, R, Jonson, B, Cumming, G, et al The concept of deadspace with special reference to the single breath test for carbon dioxide. Br J Anaesth 1981;53,77-88[Abstract/Free Full Text]
  37. Bland, JM, Altman, DG Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1,307-310[CrossRef][ISI][Medline]
  38. Tulla, H, Takala, J, Alhava, E, et al Respiratory changes after open-heart surgery. Intensive Care Med 1991;17,365-369[CrossRef][ISI][Medline]
  39. Talbot, F Basal metabolism standards. Am J Dis Child 1938;55,455-459
  40. Bernard, GR, Artigas, A, Brigham, KL, et al The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994;149,818-824[Abstract]
  41. Nuckton, TJ, Alonso, JA, Kallet, RH, et al Pulmonary dead-space fraction as a risk factor for death in the acute respiratory distress syndrome. N Engl J Med 2002;346,1281-1286[Abstract/Free Full Text]
  42. Rubin, DB, Wiener-Kronish, JP, Murray, JF, et al Elevated von Willebrand factor antigen is an early plasma predictor of acute lung injury in nonpulmonary sepsis syndrome. J Clin Invest 1990;86,474-480[ISI][Medline]
  43. Ware, LB, Conner, ER, Matthay, MA von Willebrand factor antigen is an independent marker of poor outcome in patients with early acute lung injury. Crit Care Med 2001;29,2325-2331[CrossRef][ISI][Medline]
  44. Fletcher, R Relationship between alveolar deadspace and arterial oxygenation in children with congenital cardiac disease. Br J Anaesth 1989;62,168-176[Abstract/Free Full Text]
  45. Severinghaus, J, Stupfel, M Alveolar dead space as an index of distribution of blood flow in pulmonary capillaries. J Appl Physiol 1957;10,335-348[Abstract/Free Full Text]
  46. Cooper, E Physiological dead-space in passive ventilation: relationship with tidal volume, frequency, age, and minor upsets of respiratory health. Anesth Analg 1967;22,119-220
  47. Bohr, C Über die Lungenatmung. Scand Arch Physiol 1891;2,236-268
  48. Enghoff, H Volumen inefficax: Bemerkungen zur Frage des schädlichen Raumes. Upsalla Läkarefören Förhandl 1938;44,119-218




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