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Findings on the Portable Chest Radiograph Correlate with Fluid Balance in Critically Ill Patients
Findings on the Portable Chest Radiograph Correlate With Fluid Balance in Critically Ill Patients* Greg S. Martin, MD, FCCP; E. Wesley Ely, MD, MPH, FCCP; Frank E. Carroll, MD; and Gordon R. Bernard, MD, FCCP
Study objectives: Fluid balance concerns occur daily in critically ill patients, complicated by difficulties assessing intravascular volume. Chest radiographs (CXRs) quantify pulmonary edema in acute lung injury (ALI) and total blood volume in normal subjects. We hypothesized that CXRs would reflect temporal changes in fluid balance in critically ill patients. Design: Standardized scoring of 133 supine, portable, anteroposterior CXRs. Outcomes included subjective and objective measures of intravascular volume and pulmonary edema. Setting: Academic university medical center and affiliated Veterans Affairs hospital. Patients: Thirty-seven patients with ALI receiving mechanical ventilation blindly randomized to treatment with diuretics and colloids or dual placebo for 5 days. Measurements and results: Treated patients experienced a 3.3-L diuresis and 10-kg weight loss during the 5-day period. A significant correlation was observed in all patients between changes in vascular pedicle width (VPW) and net intake/output (r ⴝ 0.50, p ⴝ 0.01) or weight (r ⴝ 0.51, p ⴝ 0.01). The correlation between VPW and fluid balance was greatest for weight changes in the treatment group alone (r ⴝ 0.71, p ⴝ 0.005). Pulmonary artery occlusion pressure correlated highly with changes in VPW (r ⴝ 0.70, p < 0.001). After day 1, CXRs revealed significant between-group differences in VPW without changes in cardiothoracic ratio or subjective measures of edema. The proportion of patients with VPW < 70 mm did not differ at baseline but was significantly more in the treatment group on all subsequent days (p < 0.05). Conclusions: We conclude that temporal fluid balance changes are reflected on commonly utilized portable CXRs. Objective radiographic measures of intravascular volume may be more appropriate indicators of fluid balance than subjective measures, with VPW appearing most sensitive. If systematically quantitated, serial CXRs provide a substantial supplement to other clinically available data for the purpose of fluid management in critically ill patients. (CHEST 2002; 122:2087–2095) Key words: albumins; ARDS; diuretics; fluid shifts; intensive care; mechanical ventilation; thoracic radiography Abbreviations: ALI ⫽ acute lung injury; APACHE ⫽ acute physiology and chronic health evaluation; COP ⫽ colloid osmotic pressure; CTR ⫽ cardiothoracic ratio; CVP ⫽ central venous pressure; CXR ⫽ chest radiograph; LIS ⫽ lung injury score; PAC ⫽ pulmonary artery catheter; PAOP ⫽ pulmonary artery occlusion pressure; VPW ⫽ vascular pedicle width
the intravascular volume status of critiA ssessing cally ill patients can be exceedingly difficult, 1–3
yet efforts to manipulate fluid balance occur daily in *From the Division of Pulmonary and Critical Care Medicine (Dr. Martin), Emory University School of Medicine, Atlanta, GA; and the Division of Allergy, Pulmonary and Critical Care Medicine (Drs. Ely and Bernard), and Department of Radiology and Radiologic Sciences (Dr. Carroll), Vanderbilt University School of Medicine, Nashville, TN. Supported by grants HL 07123 (Dr. Martin), HL 67739 (Dr. Martin), and AG 01023 (Dr. Ely) from the National Institutes of Health, and the AFAR Pharmacology in Aging Grant, Paul Beeson Faculty Scholar Award, and Geriatric Research and Education scholar award (Dr. Ely). Manuscript received October 10, 2001; revision accepted April 19, 2002. Correspondence to: Greg S. Martin, MD, 69 Jesse Hill Jr. Dr SE, Room 2D-004, Atlanta, GA 30335; e-mail: Greg_Martin@ Emory.org www.chestjournal.org
the ICU. Furthermore, this patient population exhibits reductions in colloid osmotic pressure (COP), often leading to impaired fluid-handling abilities and total body fluid excess.4 As such, ICU patients often For editorial comment see page 1879 require invasive hemodynamic monitoring, a circumstance predisposed to misinterpretation, of controversial benefit, and clear potential to produce harm.5– 8 Therefore, the ability to discriminate changes in fluid balance noninvasively would be of the highest clinical utility to the practicing intensivist. Chest radiographs (CXRs) have been employed for more than a century and are the most commonly used noninvasive tool for identifying and quantifying CHEST / 122 / 6 / DECEMBER, 2002
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the severity of pulmonary edema.9,10 Milne and colleagues11 defined radiographic criteria to improve differentiation between cardiogenic, renal, and injury patterns of edema. Similar investigations have shown that vascular pedicle width (VPW) correlates with total blood volume (r ⫽ 0.80) and changes in volume status (r ⫽ 0.93) on upright CXRs in patients with cardiac disease,12 and that VPW correlates well with rapid changes in total blood volume but not consistently with vascular pressure.13 Measurable changes in intravascular volume attributable to hemodialysis are accurately quantified by changes in both VPW and cardiothoracic ratio (CTR).14 Using portable CXRs, Thomason et al15 defined additional criteria to distinguish pulmonary edema patterns, reporting that a combined CTR ⬎ 0.52 and VPW ⬎ 63 mm improves overall diagnostic accuracy to 73% for hydrostatic pulmonary edema. Focusing on intravascular volume status with or without pulmonary edema, Ely and colleagues16 refined the criteria relating radiographic findings to invasive vascular pressure measurements (pulmonary artery occlusion pressure [PAOP]) in 100 ICU patients, reporting a VPW ⬎ 70 mm and CTR ⬎ 0.55 as the best discriminators of PAOP ⬎ 18 mm Hg. Given that vascular pressure measures do not perfectly translate to intravascular volume, and the association between severity of radiographic abnormalities and extravascular lung water (ie, pulmonary edema) is moderate,9,17 the ability of the radiograph to predict changes in fluid balance is unknown. Maximizing the information from readily available CXRs in ICU patients to evaluate both pulmonary edema and intravascular volume could improve outcomes.18 There are no published reports describing the radiographic manifestations of temporal fluid balance changes in critically ill patients. We hypothesized that changes in fluid balance over time would be reflected in findings that are readily available on CXRs in ICU patients. In addition, we sought to determine if the CXR could provide similar information to that available from invasive hemodynamic monitoring. To test this hypothesis, we blindly read and scored 133 supine, portable anteroposterior CXRs from 36 acute lung injury (ALI) and ARDS patients receiving mechanical ventilation. Materials and Methods This investigation was approved by the institutional review boards of Vanderbilt University Medical Center and Nashville Veterans Affairs Medical Center, and informed consent was obtained for each patient. Study Design Patients in this study were part of a prospective investigation conducted from 1996 to 1999, in which ALI/ARDS patients were 2088
randomized to blinded administration of albumin plus furosemide or dual placebo, as previously described.19,20 Demographic characteristics, severity of illness (acute physiology and chronic health evaluation [APACHE] III) and severity of ALI/ ARDS (lung injury score [LIS]) were recorded (Table 1).21–23 CXRs from each patient were examined on study days 0 (study entry), 1, 3, and 5 (end of treatment). When multiple daily CXRs were available for a given day, the first CXR for that day was chosen for evaluation. A standardized method of interpreting each CXR (see Appendix) was employed based on established methods.15,24,25 The VPW was measured by dropping a perpendicular line from the point at which the left subclavian artery exits the aortic arch, and measuring across to the point at which the superior vena cava crosses the right mainstem bronchus. The CTR was calculated by dividing the widest transverse diameter of the cardiac silhouette by the widest transverse diameter of the thorax above the diaphragm (Fig 1). CXRs were interpreted by one experienced thoracic radiologist (F.E.C.), who was unaware of any clinical-related or treatment-related variables. Each CXR
Table 1—Demographic and Physiologic Characteristics of Patients at Baseline* Characteristics
Placebo (n ⫽ 18)
Treatment (n ⫽ 19)
Demographics Mean age (SD), yr 42.5 (18.0) 42.3 (15.9) Male sex, % 74 53 ALI etiology, No. (%) Trauma 15 (54) 13 (46) Pneumonia 1 (17) 5 (83) Sepsis 1 (50) 1 (50) Aspiration 1 (100) 0 (0) Physiology, mean (SD) LIS† 2.6 (0.4) 2.6 (0.6) APACHE III score 55.8 (20.8) 61.1 (22.2) Serum total protein, g/dL 4.0 (0.5) 3.9 (0.6) Serum albumin, g/dL 1.7 (0.3) 1.8 (0.3) Minute ventilation, L/min 11.0 (3.4) 11.3 (2.7) Fio2 0.45 (0.09) 0.46 (0.09) Pao2/Fio2 ratio, mm Hg 197 (54) 179 (59) PEEP, cm H2O 10.0 (4.1) 9.0 (3.9) Paw, cm H2O 16.3 (1.2) 14.3 (1.1) Oxygenation index, cm H2O/mm Hg 8.4 (0.6) 9.7 (1.1) Peak inspiratory pressure, cm H2O 35.4 (8.1) 32.8 (7.4) Plateau inspiratory pressure, cm 28.0 (4.8) 27.2 (4.0) H2O Cstat, mL/cm H2O 31 (11) 31 (14) Vd/Vt 0.42 (0.10) 0.43 (0.18) Mean tidal volume, mL 576 (180) 530 (165) VPW, mm 65.1 (16.0) 61.0 (9.1) CTR 0.53 (0.06) 0.54 (0.06) Edema score 2.1 (0.8) 1.9 (0.8) Septal lines 0.1 (0.3) 0.1 (0.2) Barotrauma 0.5 (0.5) 0.6 (0.5) Quadrants 3.6 (0.6) 3.8 (0.4) CVP, mm Hg 11.1 (6.8) 10.8 (4.8) PAOP, mm Hg 17.4 (6.4) 15.3 (3.4) Cardiac output, L/min 8.2 (2.7) 10.3 (3.6) *Data are presented as No. (%) unless otherwise indicated. Fio2 ⫽ fraction of inspired oxygen; PEEP ⫽ positive end-expiratory pressure; Paw ⫽ mean airway pressure; Cstat ⫽ static respiratory system compliance; Vd/Vt ⫽ alveolar dead space fraction. †From Murray et al.22 Clinical Investigations in Critical Care
resolution in a full 14- by 17-inch format with computerized calipers used for objective radiographic measures (VPW, CTR). Statistical Analysis The primary outcome variable was VPW, with secondary variables including CTR, edema score (0 to 4 discrete variable as previously defined25,26), and the presence and severity of septal lines (short straight lines perpendicular to and abutting the lateral pleural edge, 1 to 2 cm in length) and barotrauma. Data presented are mean ⫾ SD, and were analyzed using software (NCSS Version 6.0; NCSS Statistical Software; Kaysville, UT).27 When comparisons between treatment groups was performed, assignment was made on an intent-to-treat basis. Continuous variable measurements were compared using analysis of variance, with t tests or Mann-Whitney U tests for normally or nonnormally distributed data, respectively, using Bonferroni correction for multiple comparisons when appropriate. The Fisher exact test was chosen for dichotomous variables, and the 2 statistic with Yates correction was used for analysis of proportions. Univariate linear regression was employed for correlation of continuous variables. An ␣ value of 0.05 was chosen to indicate statistical significance.
Results
Figure 1. Pictorial representation of landmarks by which to measure VPW and CTR on a routine CXR. Point 1 is the origin of the left subclavian artery as it exits the aortic arch. Point 2 represents the superior vena cava crossing the right mainstem bronchus. VPW is calculated between the perpendicular lines separating these two points. CTR is calculated by dividing the maximum cardiac width by the maximum thoracic width.
was randomly numbered, and demographic details or any information regarding treatment assignment was obscured, after which it was examined specifically to determine if sufficient quality and exposure permitted valid interpretation. Radiographic Methods Conventional 14- by 17-inch portable, supine, anteroposterior CXRs were exposed on TMLO film used in an x-omatic cassette (Kodak Corporation; Rochester, NY) were obtained for each patient prior to October 1997. The typical radiographic technique involved a 40-inch focal film distance, 75 to 85 kilovoltage peak, and a typical 1 mA-s exposure adjusted to patient body habitus. Each CXR was processed in a standard rapid processor with a processor time of 45 s. After October 1997, all CXRs were obtained in a computed radiography format using photostimulable reusable image media plates (AGFA Corporation; Ridgefield Park, NJ). Each was exposed in standard 14- by 17-inch computed radiography cassettes with similar focal film distance at a 75 kilovoltage peak and variable milliampere-seconds (based on body habitus). Processing was performed in a laser scanning reader (model ADC70; AFGA Corporation) attached to a picture archival and communication system. Each radiograph was displayed for interpretation on a workstation at 2,000 by 2,500 www.chestjournal.org
Thirty-seven patients were enrolled and completed the study protocol. CXRs from 1 treated patient were unavailable, yielding 36 patients for subsequent analysis (treatment, n ⫽ 18; control, n ⫽ 18). Eleven subsequent daily CXRs were unavailable (treatment, n ⫽ 6; control, n ⫽ 5), resulting in interpretation of 133 supine, portable, anteroposterior CXRs. There were no significant differences in any measured variable comparing the analog and digital radiographic formats. Randomization groups were similar demographically and by severity of illness (LIS and APACHE III). ALI/ARDS was most commonly associated with trauma, pneumonia, and sepsis. All patients in the treatment group experienced fluid loss, with a mean 3.3-L net diuresis and significantly higher urine output than the control group, which gained 0.5 L over the 5-day treatment period (p ⫽ 0.14). This was accompanied by a mean weight loss of 10.0 kg over 5 days in the treatment group vs a weight loll of 4.7 kg in the control group (p ⫽ 0.04). Changes in weight were evident by day 1 (⫺ 2.8 kg vs ⫺ 0.8 kg, respectively; p ⫽ 0.05) without significant change in net intake/output until subsequent days (Table 2). Patients in the treatment group achieved a mean 1.9 g/dL increase in serum total protein during the 5-day treatment protocol, while control patients increased by only 0.7 g/dL (p ⬍ 0.001). There was no significant difference in ventilator management or mortality between groups. None of the radiographic measures of edema (see Appendix), including VPW and CTR, were significantly different between groups at baseline. During CHEST / 122 / 6 / DECEMBER, 2002
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Table 2—Change in Outcome Variables During the Study Period* Control Subjects (n ⫽ 18) Variables Body weight, kg Net fluid balance, L Serum total protein, g/dL VPW, mm CTR Edema score Septal lines Barotrauma Quadrants Tidal volume, mL Pao2/Fio2, mm Hg PEEP, cm H2O Peak inspiratory pressure, cm H2O Plateau inspiratory pressure, cm H2O Cstat, mL/cm H2O Vd/Vt LIS‡
Treatment Patients (n ⫽ 18)
Day 1
Day 3
Day 5
Day 1
Day 3
Day 5
⫺ 0.8 (1.6) 0.6 (2.5) 0.0 (0.2) 0.2 (5.4) ⫺ 0.01 (0.04) 0.1 (0.4) 0.0 (0.1) 0.0 (0.2) 0.3 (0.3) ⫺ 15 (48) 5 (25) 0.3 (1.5) 1.3 (7.4) ⫺ 0.6 (1.6) ⫺ 0.2 (9.2) 0.00 (0.26) 0.1 (0.2)
⫺ 2.4 (6.3) 0.9 (5.4) 0.2 (0.4) ⫺ 0.7 (5.2) ⫺ 0.01 (0.06) ⫺ 0.1 (0.3) ⫺ 0.1 (0.2) ⫺ 0.1 (0.3) 0.1 (0.6) 36 (46) 43 (84) ⫺ 0.7 (1.4) 3.3 (8.1) ⫺ 2.4 (0.6) 2.6 (9.1) ⫺ 0.04 (0.09) ⫺ 0.3 (0.3)
⫺ 4.7 (8.8) 0.5 (1.0) 0.7 (0.6) 1.9 (6.8) ⫺ 0.01 (0.04) ⫺ 0.6 (0.6) ⫺ 0.1 (0.1) ⫺ 0.2 (0.4) 0.0 (0.8) 11 (49) 52 (112) ⫺ 1.2 (2.3) ⫺ 2.2 (11.3) ⫺ 0.1 (2.8) ⫺ 0.6 (10.6) 0.01 (0.12) ⫺ 0.3 (0.4)
⫺ 2.8 (3.1) ⫺ 0.1 (2.9) 0.6 (0.3) ⫺ 2.3 (6.1) 0.00 (0.08) ⫺ 0.1 (0.4) 0.0 (0.1) 0.0 (0.2) ⫺ 0.3 (1.0) 25 (61) 64 (73) ⫺ 1.0 (1.1) ⫺ 1.3 (5.8) ⫺ 1.0 (1.3) 1.9 (6.5) ⫺ 0.11 (0.14) ⫺ 0.3 (0.3)
⫺ 6.7 (5.2) ⫺ 2.1 (5.0) 1.6 (0.4)† ⫺ 5.1 (6.2)† ⫺ 0.01 (0.08) 0.0 (0.5) ⫺ 0.1 (0.1) ⫺ 0.2 (0.4) ⫺ 0.2 (0.9) 55 (73) 47 (82) ⫺ 1.8 (0.9) 0.2 (6.1) ⫺ 1.1 (1.5) 6.7 (16.5) ⫺ 0.01 (0.16) ⫺ 0.3 (0.4)
⫺ 10.0 (5.6)† ⫺ 3.3 (1.1)† 1.9 (0.5)† ⫺ 5.3 (7.6)† 0.00 (0.06) ⫺ 0.5 (0.5) ⫺ 0.1 (0.1) ⫺ 0.3 (0.3) ⫺ 0.6 (1.0) 57 (70) 45 (88) ⫺ 1.6 (1.5) 0.8 (6.6) ⫺ 2.0 (1.1) 1.0 (11.3) ⫺ 0.03 (0.16) ⫺ 0.3 (0.5)
*Primary outcome variables measured during the study period, stratified by randomization group. Data presented are mean (SD). See Table 1 for expansion of abbreviations. †Statistically significant difference compared to baseline at p ⬍ 0.05 level. ‡From Murray et al.22
the 5-day treatment period, VPW was significantly reduced in treated patients (⫺ 5.2 mm by day 5, p ⫽ 0.04; Fig 2). VPW in this group was significantly less at day 3 (p ⫽ 0.04) and day 5 (p ⫽ 0.01) vs the control group (Table 2). CTR did not change significantly from baseline during the 5-day treatment
period. No other measured variables changed significantly over time within or between groups. Representative measurements of VPW and CTR at baseline and day 5 are presented graphically in Figure 3, top and bottom. Intravascular volume, as estimated from PAOP,
Figure 2. Graphical representation of changes in VPW over time. Points represent mean values with error bars depicting SEM (mean ⫾ SEM) at each time point. *Significant within-group change from baseline; †Time points with significant between-group differences. 2090
Clinical Investigations in Critical Care
The correlation statistic was greatest between VPW and changes in weight for patients in the treatment group (r ⫽ 0.71, p ⫽ 0.005). Regarding subjective radiographic signs, there were no significant differences in the assessment of cardiomegaly or density of infiltrates, edema score, presence or absence of septal lines, peribronchial cuffing, barotrauma, pleural effusions, or air bronchograms (Table 2). This group of patients with ALI rarely manifested the classic descriptions of a “patchy or peripheral” edema pattern; rather, ⬎ 90% had diffuse symmetric lung densities. There was no significant correlation between changes in radiographic edema score and changes in VPW. In addition, there was no correlation between radiographic findings and either etiology of lung injury or overall outcome, including mortality, days of mechanical ventilation, and length of ICU or hospital stay.
Discussion
Figure 3. Top: Portable, supine CXR at study entry from a patient with trauma-related ALI/ARDS. Markers depict measurements of VPW and CTR at baseline. Bottom: Portable, supine CXR from the same patient at day 5 after diuresis of 6.5 L and 8-kg weight loss accompanied by 68% increase in serum albumin concentration. Markers depict measurements of VPW and CTR at end of therapy.
correlated strongly with changes in VPW from baseline to day 5 in the subset of patients with pulmonary artery catheter (PAC) measurements over the 5-day period (n ⫽ 10, r ⫽ 0.70, p ⬍ 0.001). The relationship between changes in central venous pressure (CVP) and VPW over the 5-day period was also significant (r ⫽ 0.56, p ⬍ 0.001). There was no significant correlation between changes in CTR or edema scoring and measured intravascular volume. Regarding objectively measured radiographic signs, the proportion of treated patients with VPW exceeding either of the reported thresholds for hydrostatic edema (ie, 63 mm or 70 mm) was significantly less on every day after study entry (p ⬍ 0.05 for each day). Conversely, the fraction of patients exceeding the 0.52 or 0.55 threshold for CTR was similar within and between groups at all time points. A significant correlation was found in all patients between changes in VPW and net intake/output (r ⫽ 0.50, p ⫽ 0.01) or weight (r ⫽ 0.51, p ⫽ 0.01). www.chestjournal.org
Fluid balance is one of the most frequently manipulated clinical care variables in the ICU. The risks associated with invasive monitoring and its relationship to heightened mortality make the evaluation and utilization of other modalities for tracking volume status in critically ill patients vitally important. In this blinded systematic evaluation of portable CXRs in the ICU, we have shown that changes in fluid balance are reflected radiographically in critically ill patients. More importantly, radiographic changes in VPW correlate highly with invasive measures of intravascular volume by PAC. Considering the consistency of the findings of this and two previous investigations15,16 of portable supine CXRs, we believe the VPW represents an underutilized radiographic tool that could aid clinicians in their daily assessment of intravascular volume status. Intravascular volume status and fluid balance are essential components of ICU patient management that relate to clinical outcome.4,28 However, the ability to predict changes in fluid balance is particularly challenging in patients with excess lung water and “normal” hydrostatic pressures, such as ALI/ ARDS. This clinical syndrome remains relatively common among ICU patients and carries an associated high mortality.29 Despite a well-established association between fluid retention and weight gain with mortality in ARDS,4,28,30 –32 little is known about the physiologic effects of intravascular volume reduction in these patients. Retrospective analyses suggest improved survival with temporal decrements in hydrostatic pressures,31 with negative fluid balance being a strong predictor of survival in a broader group of critically ill patients.33 A prospective trial CHEST / 122 / 6 / DECEMBER, 2002
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randomizing patients with pulmonary edema to a fluid-restrictive strategy found reductions in duration of mechanical ventilation and ICU stay.34 Given that 82% of patients with ALI may manifest increased hydrostatic pressures at least intermittently, using the VPW as an aid in monitoring fluid balance may be immediately clinically applicable.35 From the current data, we conclude that readily available radiographic measures are representative of changes in intravascular volume in critically ill patients. Furthermore, objective radiographic measurements of the VPW may be a better indicator of volume status than more frequently used traditional subjective measurements (eg, quadrant counting or edema grading), which did not change significantly in this investigation despite marked shifts in fluid balance. Importantly, diuresis with resultant weight loss is radiographically evident in patients with ALI through reductions in VPW. These data suggest that roughly half of the changes in fluid balance or weight in patients with ALI treated with colloids and diuretics are detected radiographically by changes in VPW. However, it must be emphasized that intake/output and body weight may vary substantially without obvious cause. Great care was taken in this study to capture all measurable changes in fluid balance and body weight, thus allowing at least moderate correlations between body weight, net fluid balance, and VPW. Despite strict attention to such data, a substantial disparity exists between fluid balance and weight change.36 The most logical explanation for this is the difficulty in quantifying insensible fluid losses in critically ill patients, thus promoting weight as the simpler and more accurate fluid balance variable. In standard clinical settings where fluid balance parameters are tracked much less rigorously, sequential evaluation of the VPW could allow for easier and more reproducible determination of changes in intravascular volume. This is supported by the high interrater and intrarater correlation coefficients for measuring VPW.15,16 The relevance of these findings relates to the difficulty in determining intravascular volume in critically ill patients1–3 and the ready availability of radiographs in ICU patients. The majority of CXRs obtained from ICU patients receiving mechanical ventilation result in a change in therapy (66%), with the most frequent intervention being institution of diuretic therapy.37 This attests to the fact that physicians commonly incorporate CXR findings into management decisions regarding volume status, perhaps without fully understanding or maximizing their interpretation. For example, the accuracy of radiographically differentiating hydrostatic from permeability pulmonary edema is improved from 41 to 70% with the inclusion of VPW and CTR.15,16 Combining 2092
data from other modalities in the assessment of intravascular volume may be necessary. The majority of strategies designed to assess intravascular volume have shown limited success or resulted in substantial increases in resource utilization from other diagnostic modalities.18,38 Yet, these diagnostic algorithms have generally failed to incorporate readily available complementary information available from CXRs, such as the VPW. These data establish that CXRs are similarly sensitive to changes in invasive estimates of intravascular volume (accounting for 49% of changes in PAOP). This relationship is less well defined for CVP, which is less accurate for determination of cardiac preload or intravascular volume. As with discrepancies between fluid balance and body weight changes, intravascular volume may be affected by external variables, such as plasma COP or capillary permeability, which may continuously affect intravascular volume. Invasive measurements available from pulmonary artery catheterization provide pressure measures from which volume may be extrapolated (eg, PAOP as a measure of left ventricular end-diastolic volume). These pressure measures are influenced substantially by changes in cardiac compliance and contractility as well as intrathoracic pressure, and thus do not solely portray changes in intravascular volume. These data suggest that the known correlation of VPW with intravascular volume in upright radiographs12,14,18 may be extended to the standard radiographs available in the ICU. Serial CXRs may thus serve as a readily available clinical tool from which to extrapolate intravascular volume information regardless of interposed variables that complicate assumptions of intravascular volume from PAC measures. For these reasons, significant weight may be attached to the VPW as a measure of intravascular volume status, supporting its use in a clinical decision model complementing traditional information, such as fluid balance, physical examination, and laboratory studies. Limitations of this investigation include the uniformity of the patient population enrolled into this investigation (ie, ALI/ARDS patients) and the use of a single radiologist for interpretation of CXRs. Spectrum bias, the enhanced sensitivity of a test for the patient population in which it was derived, would mandate that our findings be reproduced in patients without ALI/ARDS.39 The ability to discriminate VPW may be affected by parenchymal lung densities (such as in ALI),40 making this measure potentially even more useful in mechanically ventilated patients as a whole. VPW is the most sensitive noninvasive indicator of intravascular volume, as it reflects both venous (right-sided) and arterial (left-sided) structures.41 Pistolesi and colleagues12 reported that volClinical Investigations in Critical Care
ume expansion of 1.0 L resulted in widening of the VPW by 5.0 mm in erect CXRs. Though radiographically detectable, the difference noted in this population with supine, portable CXRs was less marked (ie, a 5.0-mm VPW reduction corresponded to a 3.2-L negative fluid balance), possibly due to differences in technique or overlying parenchymal densities associated with ALI. In the era of digital radiography, computerized digital calipers could allow for more accurate measures, making small reductions in VPW more readily detectable. Fifteen degrees of left anterior oblique projection may reduce VPW by 6%,24 and thus implementation of standardized radiographic techniques is important to maximize CXR interpretation, as shown by improvements in interpretative accuracy with adaptive training.42,43 Consistency of technique is apparent in Figure 3, where the degree of left anterior oblique rotation is equal between radiographs. We chose to use the PAC to assess intravascular volume because of its acceptance as the clinical “gold standard.” Despite its broad use, the inherent limitations of the PAC for hemodynamic monitoring must be noted, particularly as it relates to preload assessment. Often used for such information, the potential discrepancies in estimating vascular volumes from PAC pressure measurements must be acknowledged, as described previously. Interpreting these data, therefore, requires that clinicians recognize the potential inaccuracies in estimating intravascular volume from PAC measures. It should also be considered that all barometric measures (ie, those available from PAC) do not account for volumetric changes attributable to changes in COP. Intravascu-
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lar volume rises in tandem with increases in COP, at least partially independent of hydrostatic pressure, and thus the PAC does not specifically account for changes in COP. As such, given the changes in serum protein concentrations, true intravascular volume may have changed more or less than predicted by PAOP. In conclusion, this study provides previously unrecognized information about sequential changes in radiographic appearance during fluid balance manipulations. We have shown that objective radiographic measurement of the VPW from portable, supine CXRs, which are universally available in ICU patients, correlates highly with bedside measures of fluid balance and invasive estimates of intravascular volume. Considering the risks associated with invasive monitoring strategies and the growing complexity of algorithms including novel diagnostic modalities, refining current methods of monitoring volume status in our most critically ill patients is imperative. If confirmed in a prospective data set of a varied ICU patient population, these findings may advance the training of both radiologists and intensivists, who are currently taught little regarding objective vascular measures, such as the VPW. Exploitation of available CXR data may lead to reductions in procedurerelated adverse events and thus may improve patient outcomes without additional resource utilization, and should be tested in prospective clinical trials. ACKNOWLEDGMENT: The authors thank Linda Collins, RN, Susan Bozeman, RN, and our ICU patients and families. We also thank Drew Imhulse at Emory University for technical and artistic assistance.
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Appendix
*MR ⫽ medical record; CT ⫽ cardiothoracic; NL ⫽ normal; SVC ⫽ superior vena cava; RUQ ⫽ right upper quadrant; RLQ ⫽ right lower quadrant; LUQ ⫽ left upper quadrant; LLQ ⫽ left lower quadrant.
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teinemia predicts ARDS development, weight gain, and death in patients with sepsis. Crit Care Med 2000; 28:3137–3145 5 Bernard GR, Sopko G, Cerra F, et al. Pulmonary artery catheterization and clinical outcomes: National Heart, Lung, and Blood Institute and Food and Drug Administration Workshop Report. JAMA 2000; 283:2568 –2572 6 Al-Kharrat T, Zarich S, Amoateng-Adjepong Y, et al. Analysis of observer variability in measurement of pulmonary artery occlusion pressures. Am J Respir Crit Care Med 1999; 160:415– 420 7 Connors AF Jr, Speroff T, Dawson NV, et al. The effectiveClinical Investigations in Critical Care
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ness of right heart catheterization in the initial care of critically ill patients. JAMA 1996; 276:889 – 897 Dalen JE, Bone RC. Is it time to pull the pulmonary artery catheter? JAMA 1996; 276:916 –918 Staub NC. Clinical use of lung water measurements: report of a workshop. Chest 1986; 90:588 –594 Pistolesi M, Miniati M, Milne ENC, et al. The chest roentgenogram in pulmonary edema. Clin Chest Med 1985; 6:315–344 Milne EN, Pistolesi M, Miniati M, et al. The radiologic distinction of cardiogenic and noncardiogenic edema. AJR Am J Roentgenol 1985; 144:879 – 894 Pistolesi M, Milne EN, Miniati M, et al. The vascular pedicle and the vena azygous: II. In cardiac failure. Radiology 1984; 152:9 –17 Milne ENC. Correlation of physiologic findings with chest roentgenology. Radiol Clin North Am 1973; 11:17– 47 Don C, Burns KD, Levine DZ. Body fluid status in hemodialysis patients: the value of the chest radiograph. Can Assoc Radiol J 1990; 41:123–126 Thomason JWW, Ely EW, Chiles C, et al. Appraising pulmonary edema using supine roentgenograms in ventilated patients. Am J Respir Crit Care Med 1998; 157:1600 –1608 Ely EW, Smith AC, Chiles C, et al. The radiologic determination of volume status using portable, digital, chest radiography: a prospective investigation in 100 patients. Crit Care Med 2001; 29:1502–1512 Van der Water JM, Sheh JM, O’Connor NE, et al. Pulmonary extravascular water volume: measurement and significance in critically ill patients. J Trauma 1970; 10:440 – 449 Ely EW, Haponik EF. Using the chest radiograph to determine intravascular volume status: the role of vascular pedicle width. Chest 2002; 121:942–950 Martin GS, Mangialardi RJ, Wheeler AP, et al. Albumin and diuretics in ARDS [abstract]. Am J Respir Crit Care Med 1999; 159:A376 Martin GS, Mangialardi RJ, Wheeler AP, et al. Albumin and furosemide therapy in hypoproteinemic patients with acute lung injury. Crit Care Med 2002; 30:2175–2182 Bernard GR, Artigas A, Brigham KL, et al. The AmericanEuropean consensus conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994; 149:818 – 824 Murray JF, Matthay MA, Luce JM, et al. An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis 1988; 138:720 –723 Knaus WA, Wagner DP, Draper EA, et al. The APACHE III prognostic system: risk prediction of hospital mortality for critically ill hospitalized adults. Chest 1991; 100:1619 –1636 Milne E, Pistolesi M, Miniati M, et al. The vascular pedicle of the heart and the venous azygous: I. The normal subject. Radiology 1984; 152:1– 8 Wheeler AP, Carroll FE, Bernard GR. Radiographic issues in adult respiratory distress syndrome. New Horiz 1993; 1:471– 477
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26 Bernard GR, Wheeler AP, Russell JA, et al. The effects of ibuprofen on the physiology and survival of patients with sepsis: The Ibuprofen in Sepsis Study Group. N Engl J Med 1997; 336:912–918 27 Hintze JL. Number Cruncher Statistical Software (NCSS) 6.0 user’s manual. Kaysville, UT: NCSS, 1995 28 Simmons RS, Berdine GG, Seidenfeld JJ, et al. Fluid balance and the adult respiratory distress syndrome. Am Rev Respir Dis 1987; 135:924 –929 29 Milberg JA, Davis DR, Steinberg KP, et al. Improved survival of patients with acute respiratory distress syndrome (ARDS), 1983–1993. JAMA 1995; 273:306 –309 30 Schuster DP. The case for and against fluid restriction and occlusion pressure reduction in adult respiratory distress syndrome. New Horiz 1993; 1:478 – 488 31 Humphrey H, Hall J, Sznajder I, et al. Improved survival in ARDS patients associated with a reduction in pulmonary capillary wedge pressure. Chest 1990; 97:1176 –1180 32 Neff MJ, Rubenfeld GD, Caldwell ES, et al. Exclusion of patients with elevated pulmonary capillary wedge pressure from ARDS [abstract]. Am J Respir Crit Care Med 1999; 159:A716 33 Alsous F, Khamiees M, DeGirolamo A, et al. Negative fluid balance predicts survival in patients with septic shock: a retrospective pilot study. Chest 2000; 117:1749 –1754 34 Mitchell JP, Schuller D, Calandrino FS, et al. Improved outcome based on fluid management in critically ill patients requiring pulmonary artery catheterization. Am Rev Respir Dis 1992; 145:990 –998 35 Ferguson ND, Meade MO, Tomlinson G, et al. Values of the pulmonary artery occlusion pressure (PAOP) in ARDS and ALI [abstract]. Am J Respir Crit Care Med 1999; 159:A716 36 Roos AN, Westendorp RG, Frolich M, et al. Weight changes in critically ill patients evaluated by fluid balances and impedance measurements. Crit Care Med 1993; 21:871– 877 37 Marik PE, Janower ML. The impact of routine chest radiography on ICU management decisions: an observational study. Am J Crit Care 1997; 6:95–98 38 Duane PG, Colice GL. Impact of noninvasive studies to distinguish volume overload from ARDS in acutely ill patients with pulmonary edema. Chest 2000; 118:1709 –1717 39 Ransohoff DF, Feinstein AR. Problems of spectrum and bias in evaluating the efficacy of diagnostic tests. N Engl J Med 1978; 299:926 –930 40 Henschke CI, Yankelevitz DF, Wand A, et al. Accuracy and efficacy of chest radiography in the intensive care unit. Radiol Clin North Am 1996; 34:21–31 41 Milne ENC, Imray TJ, Pistolesi M, et al. The vascular pedicle and the vena azygos: III. In trauma—the “vanishing azygos.” Radiology 1984; 153:25–31 42 Rubenfeld GD, Caldwell E, Granton J, et al. Interobserver variability in applying a radiographic definition for ARDS. Chest 1999; 116:1347–1353 43 Meade MO, Cook RJ, Guyatt GH, et al. Interobserver variation in interpreting chest radiographs for the diagnosis of acute respiratory distress syndrome. Am J Respir Crit Care Med 2000; 161:85–90
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Study objectives: Fluid balance concerns occur daily in critically ill patients, complicated by difficulties assessing intravascular volume. Chest radiographs (CXRs) quantify pulmonary edema in acute lung injury (ALI) and total blood volume in normal subjects. We hypothesized that CXRs would reflect temporal changes in fluid balance in critically ill patients. Design: Standardized scoring of 133 supine, portable, anteroposterior CXRs. Outcomes included subjective and objective measures of intravascular volume and pulmonary edema. Setting: Academic university medical center and affiliated Veterans Affairs hospital. Patients: Thirty-seven patients with ALI receiving mechanical ventilation blindly randomized to treatment with diuretics and colloids or dual placebo for 5 days. Measurements and results: Treated patients experienced a 3.3-L diuresis and 10-kg weight loss during the 5-day period. A significant correlation was observed in all patients between changes in vascular pedicle width (VPW) and net intake/output (r ⴝ 0.50, p ⴝ 0.01) or weight (r ⴝ 0.51, p ⴝ 0.01). The correlation between VPW and fluid balance was greatest for weight changes in the treatment group alone (r ⴝ 0.71, p ⴝ 0.005). Pulmonary artery occlusion pressure correlated highly with changes in VPW (r ⴝ 0.70, p < 0.001). After day 1, CXRs revealed significant between-group differences in VPW without changes in cardiothoracic ratio or subjective measures of edema. The proportion of patients with VPW < 70 mm did not differ at baseline but was significantly more in the treatment group on all subsequent days (p < 0.05). Conclusions: We conclude that temporal fluid balance changes are reflected on commonly utilized portable CXRs. Objective radiographic measures of intravascular volume may be more appropriate indicators of fluid balance than subjective measures, with VPW appearing most sensitive. If systematically quantitated, serial CXRs provide a substantial supplement to other clinically available data for the purpose of fluid management in critically ill patients. (CHEST 2002; 122:2087–2095) Key words: albumins; ARDS; diuretics; fluid shifts; intensive care; mechanical ventilation; thoracic radiography Abbreviations: ALI ⫽ acute lung injury; APACHE ⫽ acute physiology and chronic health evaluation; COP ⫽ colloid osmotic pressure; CTR ⫽ cardiothoracic ratio; CVP ⫽ central venous pressure; CXR ⫽ chest radiograph; LIS ⫽ lung injury score; PAC ⫽ pulmonary artery catheter; PAOP ⫽ pulmonary artery occlusion pressure; VPW ⫽ vascular pedicle width
the intravascular volume status of critiA ssessing cally ill patients can be exceedingly difficult, 1–3
yet efforts to manipulate fluid balance occur daily in *From the Division of Pulmonary and Critical Care Medicine (Dr. Martin), Emory University School of Medicine, Atlanta, GA; and the Division of Allergy, Pulmonary and Critical Care Medicine (Drs. Ely and Bernard), and Department of Radiology and Radiologic Sciences (Dr. Carroll), Vanderbilt University School of Medicine, Nashville, TN. Supported by grants HL 07123 (Dr. Martin), HL 67739 (Dr. Martin), and AG 01023 (Dr. Ely) from the National Institutes of Health, and the AFAR Pharmacology in Aging Grant, Paul Beeson Faculty Scholar Award, and Geriatric Research and Education scholar award (Dr. Ely). Manuscript received October 10, 2001; revision accepted April 19, 2002. Correspondence to: Greg S. Martin, MD, 69 Jesse Hill Jr. Dr SE, Room 2D-004, Atlanta, GA 30335; e-mail: Greg_Martin@ Emory.org www.chestjournal.org
the ICU. Furthermore, this patient population exhibits reductions in colloid osmotic pressure (COP), often leading to impaired fluid-handling abilities and total body fluid excess.4 As such, ICU patients often For editorial comment see page 1879 require invasive hemodynamic monitoring, a circumstance predisposed to misinterpretation, of controversial benefit, and clear potential to produce harm.5– 8 Therefore, the ability to discriminate changes in fluid balance noninvasively would be of the highest clinical utility to the practicing intensivist. Chest radiographs (CXRs) have been employed for more than a century and are the most commonly used noninvasive tool for identifying and quantifying CHEST / 122 / 6 / DECEMBER, 2002
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the severity of pulmonary edema.9,10 Milne and colleagues11 defined radiographic criteria to improve differentiation between cardiogenic, renal, and injury patterns of edema. Similar investigations have shown that vascular pedicle width (VPW) correlates with total blood volume (r ⫽ 0.80) and changes in volume status (r ⫽ 0.93) on upright CXRs in patients with cardiac disease,12 and that VPW correlates well with rapid changes in total blood volume but not consistently with vascular pressure.13 Measurable changes in intravascular volume attributable to hemodialysis are accurately quantified by changes in both VPW and cardiothoracic ratio (CTR).14 Using portable CXRs, Thomason et al15 defined additional criteria to distinguish pulmonary edema patterns, reporting that a combined CTR ⬎ 0.52 and VPW ⬎ 63 mm improves overall diagnostic accuracy to 73% for hydrostatic pulmonary edema. Focusing on intravascular volume status with or without pulmonary edema, Ely and colleagues16 refined the criteria relating radiographic findings to invasive vascular pressure measurements (pulmonary artery occlusion pressure [PAOP]) in 100 ICU patients, reporting a VPW ⬎ 70 mm and CTR ⬎ 0.55 as the best discriminators of PAOP ⬎ 18 mm Hg. Given that vascular pressure measures do not perfectly translate to intravascular volume, and the association between severity of radiographic abnormalities and extravascular lung water (ie, pulmonary edema) is moderate,9,17 the ability of the radiograph to predict changes in fluid balance is unknown. Maximizing the information from readily available CXRs in ICU patients to evaluate both pulmonary edema and intravascular volume could improve outcomes.18 There are no published reports describing the radiographic manifestations of temporal fluid balance changes in critically ill patients. We hypothesized that changes in fluid balance over time would be reflected in findings that are readily available on CXRs in ICU patients. In addition, we sought to determine if the CXR could provide similar information to that available from invasive hemodynamic monitoring. To test this hypothesis, we blindly read and scored 133 supine, portable anteroposterior CXRs from 36 acute lung injury (ALI) and ARDS patients receiving mechanical ventilation. Materials and Methods This investigation was approved by the institutional review boards of Vanderbilt University Medical Center and Nashville Veterans Affairs Medical Center, and informed consent was obtained for each patient. Study Design Patients in this study were part of a prospective investigation conducted from 1996 to 1999, in which ALI/ARDS patients were 2088
randomized to blinded administration of albumin plus furosemide or dual placebo, as previously described.19,20 Demographic characteristics, severity of illness (acute physiology and chronic health evaluation [APACHE] III) and severity of ALI/ ARDS (lung injury score [LIS]) were recorded (Table 1).21–23 CXRs from each patient were examined on study days 0 (study entry), 1, 3, and 5 (end of treatment). When multiple daily CXRs were available for a given day, the first CXR for that day was chosen for evaluation. A standardized method of interpreting each CXR (see Appendix) was employed based on established methods.15,24,25 The VPW was measured by dropping a perpendicular line from the point at which the left subclavian artery exits the aortic arch, and measuring across to the point at which the superior vena cava crosses the right mainstem bronchus. The CTR was calculated by dividing the widest transverse diameter of the cardiac silhouette by the widest transverse diameter of the thorax above the diaphragm (Fig 1). CXRs were interpreted by one experienced thoracic radiologist (F.E.C.), who was unaware of any clinical-related or treatment-related variables. Each CXR
Table 1—Demographic and Physiologic Characteristics of Patients at Baseline* Characteristics
Placebo (n ⫽ 18)
Treatment (n ⫽ 19)
Demographics Mean age (SD), yr 42.5 (18.0) 42.3 (15.9) Male sex, % 74 53 ALI etiology, No. (%) Trauma 15 (54) 13 (46) Pneumonia 1 (17) 5 (83) Sepsis 1 (50) 1 (50) Aspiration 1 (100) 0 (0) Physiology, mean (SD) LIS† 2.6 (0.4) 2.6 (0.6) APACHE III score 55.8 (20.8) 61.1 (22.2) Serum total protein, g/dL 4.0 (0.5) 3.9 (0.6) Serum albumin, g/dL 1.7 (0.3) 1.8 (0.3) Minute ventilation, L/min 11.0 (3.4) 11.3 (2.7) Fio2 0.45 (0.09) 0.46 (0.09) Pao2/Fio2 ratio, mm Hg 197 (54) 179 (59) PEEP, cm H2O 10.0 (4.1) 9.0 (3.9) Paw, cm H2O 16.3 (1.2) 14.3 (1.1) Oxygenation index, cm H2O/mm Hg 8.4 (0.6) 9.7 (1.1) Peak inspiratory pressure, cm H2O 35.4 (8.1) 32.8 (7.4) Plateau inspiratory pressure, cm 28.0 (4.8) 27.2 (4.0) H2O Cstat, mL/cm H2O 31 (11) 31 (14) Vd/Vt 0.42 (0.10) 0.43 (0.18) Mean tidal volume, mL 576 (180) 530 (165) VPW, mm 65.1 (16.0) 61.0 (9.1) CTR 0.53 (0.06) 0.54 (0.06) Edema score 2.1 (0.8) 1.9 (0.8) Septal lines 0.1 (0.3) 0.1 (0.2) Barotrauma 0.5 (0.5) 0.6 (0.5) Quadrants 3.6 (0.6) 3.8 (0.4) CVP, mm Hg 11.1 (6.8) 10.8 (4.8) PAOP, mm Hg 17.4 (6.4) 15.3 (3.4) Cardiac output, L/min 8.2 (2.7) 10.3 (3.6) *Data are presented as No. (%) unless otherwise indicated. Fio2 ⫽ fraction of inspired oxygen; PEEP ⫽ positive end-expiratory pressure; Paw ⫽ mean airway pressure; Cstat ⫽ static respiratory system compliance; Vd/Vt ⫽ alveolar dead space fraction. †From Murray et al.22 Clinical Investigations in Critical Care
resolution in a full 14- by 17-inch format with computerized calipers used for objective radiographic measures (VPW, CTR). Statistical Analysis The primary outcome variable was VPW, with secondary variables including CTR, edema score (0 to 4 discrete variable as previously defined25,26), and the presence and severity of septal lines (short straight lines perpendicular to and abutting the lateral pleural edge, 1 to 2 cm in length) and barotrauma. Data presented are mean ⫾ SD, and were analyzed using software (NCSS Version 6.0; NCSS Statistical Software; Kaysville, UT).27 When comparisons between treatment groups was performed, assignment was made on an intent-to-treat basis. Continuous variable measurements were compared using analysis of variance, with t tests or Mann-Whitney U tests for normally or nonnormally distributed data, respectively, using Bonferroni correction for multiple comparisons when appropriate. The Fisher exact test was chosen for dichotomous variables, and the 2 statistic with Yates correction was used for analysis of proportions. Univariate linear regression was employed for correlation of continuous variables. An ␣ value of 0.05 was chosen to indicate statistical significance.
Results
Figure 1. Pictorial representation of landmarks by which to measure VPW and CTR on a routine CXR. Point 1 is the origin of the left subclavian artery as it exits the aortic arch. Point 2 represents the superior vena cava crossing the right mainstem bronchus. VPW is calculated between the perpendicular lines separating these two points. CTR is calculated by dividing the maximum cardiac width by the maximum thoracic width.
was randomly numbered, and demographic details or any information regarding treatment assignment was obscured, after which it was examined specifically to determine if sufficient quality and exposure permitted valid interpretation. Radiographic Methods Conventional 14- by 17-inch portable, supine, anteroposterior CXRs were exposed on TMLO film used in an x-omatic cassette (Kodak Corporation; Rochester, NY) were obtained for each patient prior to October 1997. The typical radiographic technique involved a 40-inch focal film distance, 75 to 85 kilovoltage peak, and a typical 1 mA-s exposure adjusted to patient body habitus. Each CXR was processed in a standard rapid processor with a processor time of 45 s. After October 1997, all CXRs were obtained in a computed radiography format using photostimulable reusable image media plates (AGFA Corporation; Ridgefield Park, NJ). Each was exposed in standard 14- by 17-inch computed radiography cassettes with similar focal film distance at a 75 kilovoltage peak and variable milliampere-seconds (based on body habitus). Processing was performed in a laser scanning reader (model ADC70; AFGA Corporation) attached to a picture archival and communication system. Each radiograph was displayed for interpretation on a workstation at 2,000 by 2,500 www.chestjournal.org
Thirty-seven patients were enrolled and completed the study protocol. CXRs from 1 treated patient were unavailable, yielding 36 patients for subsequent analysis (treatment, n ⫽ 18; control, n ⫽ 18). Eleven subsequent daily CXRs were unavailable (treatment, n ⫽ 6; control, n ⫽ 5), resulting in interpretation of 133 supine, portable, anteroposterior CXRs. There were no significant differences in any measured variable comparing the analog and digital radiographic formats. Randomization groups were similar demographically and by severity of illness (LIS and APACHE III). ALI/ARDS was most commonly associated with trauma, pneumonia, and sepsis. All patients in the treatment group experienced fluid loss, with a mean 3.3-L net diuresis and significantly higher urine output than the control group, which gained 0.5 L over the 5-day treatment period (p ⫽ 0.14). This was accompanied by a mean weight loss of 10.0 kg over 5 days in the treatment group vs a weight loll of 4.7 kg in the control group (p ⫽ 0.04). Changes in weight were evident by day 1 (⫺ 2.8 kg vs ⫺ 0.8 kg, respectively; p ⫽ 0.05) without significant change in net intake/output until subsequent days (Table 2). Patients in the treatment group achieved a mean 1.9 g/dL increase in serum total protein during the 5-day treatment protocol, while control patients increased by only 0.7 g/dL (p ⬍ 0.001). There was no significant difference in ventilator management or mortality between groups. None of the radiographic measures of edema (see Appendix), including VPW and CTR, were significantly different between groups at baseline. During CHEST / 122 / 6 / DECEMBER, 2002
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Table 2—Change in Outcome Variables During the Study Period* Control Subjects (n ⫽ 18) Variables Body weight, kg Net fluid balance, L Serum total protein, g/dL VPW, mm CTR Edema score Septal lines Barotrauma Quadrants Tidal volume, mL Pao2/Fio2, mm Hg PEEP, cm H2O Peak inspiratory pressure, cm H2O Plateau inspiratory pressure, cm H2O Cstat, mL/cm H2O Vd/Vt LIS‡
Treatment Patients (n ⫽ 18)
Day 1
Day 3
Day 5
Day 1
Day 3
Day 5
⫺ 0.8 (1.6) 0.6 (2.5) 0.0 (0.2) 0.2 (5.4) ⫺ 0.01 (0.04) 0.1 (0.4) 0.0 (0.1) 0.0 (0.2) 0.3 (0.3) ⫺ 15 (48) 5 (25) 0.3 (1.5) 1.3 (7.4) ⫺ 0.6 (1.6) ⫺ 0.2 (9.2) 0.00 (0.26) 0.1 (0.2)
⫺ 2.4 (6.3) 0.9 (5.4) 0.2 (0.4) ⫺ 0.7 (5.2) ⫺ 0.01 (0.06) ⫺ 0.1 (0.3) ⫺ 0.1 (0.2) ⫺ 0.1 (0.3) 0.1 (0.6) 36 (46) 43 (84) ⫺ 0.7 (1.4) 3.3 (8.1) ⫺ 2.4 (0.6) 2.6 (9.1) ⫺ 0.04 (0.09) ⫺ 0.3 (0.3)
⫺ 4.7 (8.8) 0.5 (1.0) 0.7 (0.6) 1.9 (6.8) ⫺ 0.01 (0.04) ⫺ 0.6 (0.6) ⫺ 0.1 (0.1) ⫺ 0.2 (0.4) 0.0 (0.8) 11 (49) 52 (112) ⫺ 1.2 (2.3) ⫺ 2.2 (11.3) ⫺ 0.1 (2.8) ⫺ 0.6 (10.6) 0.01 (0.12) ⫺ 0.3 (0.4)
⫺ 2.8 (3.1) ⫺ 0.1 (2.9) 0.6 (0.3) ⫺ 2.3 (6.1) 0.00 (0.08) ⫺ 0.1 (0.4) 0.0 (0.1) 0.0 (0.2) ⫺ 0.3 (1.0) 25 (61) 64 (73) ⫺ 1.0 (1.1) ⫺ 1.3 (5.8) ⫺ 1.0 (1.3) 1.9 (6.5) ⫺ 0.11 (0.14) ⫺ 0.3 (0.3)
⫺ 6.7 (5.2) ⫺ 2.1 (5.0) 1.6 (0.4)† ⫺ 5.1 (6.2)† ⫺ 0.01 (0.08) 0.0 (0.5) ⫺ 0.1 (0.1) ⫺ 0.2 (0.4) ⫺ 0.2 (0.9) 55 (73) 47 (82) ⫺ 1.8 (0.9) 0.2 (6.1) ⫺ 1.1 (1.5) 6.7 (16.5) ⫺ 0.01 (0.16) ⫺ 0.3 (0.4)
⫺ 10.0 (5.6)† ⫺ 3.3 (1.1)† 1.9 (0.5)† ⫺ 5.3 (7.6)† 0.00 (0.06) ⫺ 0.5 (0.5) ⫺ 0.1 (0.1) ⫺ 0.3 (0.3) ⫺ 0.6 (1.0) 57 (70) 45 (88) ⫺ 1.6 (1.5) 0.8 (6.6) ⫺ 2.0 (1.1) 1.0 (11.3) ⫺ 0.03 (0.16) ⫺ 0.3 (0.5)
*Primary outcome variables measured during the study period, stratified by randomization group. Data presented are mean (SD). See Table 1 for expansion of abbreviations. †Statistically significant difference compared to baseline at p ⬍ 0.05 level. ‡From Murray et al.22
the 5-day treatment period, VPW was significantly reduced in treated patients (⫺ 5.2 mm by day 5, p ⫽ 0.04; Fig 2). VPW in this group was significantly less at day 3 (p ⫽ 0.04) and day 5 (p ⫽ 0.01) vs the control group (Table 2). CTR did not change significantly from baseline during the 5-day treatment
period. No other measured variables changed significantly over time within or between groups. Representative measurements of VPW and CTR at baseline and day 5 are presented graphically in Figure 3, top and bottom. Intravascular volume, as estimated from PAOP,
Figure 2. Graphical representation of changes in VPW over time. Points represent mean values with error bars depicting SEM (mean ⫾ SEM) at each time point. *Significant within-group change from baseline; †Time points with significant between-group differences. 2090
Clinical Investigations in Critical Care
The correlation statistic was greatest between VPW and changes in weight for patients in the treatment group (r ⫽ 0.71, p ⫽ 0.005). Regarding subjective radiographic signs, there were no significant differences in the assessment of cardiomegaly or density of infiltrates, edema score, presence or absence of septal lines, peribronchial cuffing, barotrauma, pleural effusions, or air bronchograms (Table 2). This group of patients with ALI rarely manifested the classic descriptions of a “patchy or peripheral” edema pattern; rather, ⬎ 90% had diffuse symmetric lung densities. There was no significant correlation between changes in radiographic edema score and changes in VPW. In addition, there was no correlation between radiographic findings and either etiology of lung injury or overall outcome, including mortality, days of mechanical ventilation, and length of ICU or hospital stay.
Discussion
Figure 3. Top: Portable, supine CXR at study entry from a patient with trauma-related ALI/ARDS. Markers depict measurements of VPW and CTR at baseline. Bottom: Portable, supine CXR from the same patient at day 5 after diuresis of 6.5 L and 8-kg weight loss accompanied by 68% increase in serum albumin concentration. Markers depict measurements of VPW and CTR at end of therapy.
correlated strongly with changes in VPW from baseline to day 5 in the subset of patients with pulmonary artery catheter (PAC) measurements over the 5-day period (n ⫽ 10, r ⫽ 0.70, p ⬍ 0.001). The relationship between changes in central venous pressure (CVP) and VPW over the 5-day period was also significant (r ⫽ 0.56, p ⬍ 0.001). There was no significant correlation between changes in CTR or edema scoring and measured intravascular volume. Regarding objectively measured radiographic signs, the proportion of treated patients with VPW exceeding either of the reported thresholds for hydrostatic edema (ie, 63 mm or 70 mm) was significantly less on every day after study entry (p ⬍ 0.05 for each day). Conversely, the fraction of patients exceeding the 0.52 or 0.55 threshold for CTR was similar within and between groups at all time points. A significant correlation was found in all patients between changes in VPW and net intake/output (r ⫽ 0.50, p ⫽ 0.01) or weight (r ⫽ 0.51, p ⫽ 0.01). www.chestjournal.org
Fluid balance is one of the most frequently manipulated clinical care variables in the ICU. The risks associated with invasive monitoring and its relationship to heightened mortality make the evaluation and utilization of other modalities for tracking volume status in critically ill patients vitally important. In this blinded systematic evaluation of portable CXRs in the ICU, we have shown that changes in fluid balance are reflected radiographically in critically ill patients. More importantly, radiographic changes in VPW correlate highly with invasive measures of intravascular volume by PAC. Considering the consistency of the findings of this and two previous investigations15,16 of portable supine CXRs, we believe the VPW represents an underutilized radiographic tool that could aid clinicians in their daily assessment of intravascular volume status. Intravascular volume status and fluid balance are essential components of ICU patient management that relate to clinical outcome.4,28 However, the ability to predict changes in fluid balance is particularly challenging in patients with excess lung water and “normal” hydrostatic pressures, such as ALI/ ARDS. This clinical syndrome remains relatively common among ICU patients and carries an associated high mortality.29 Despite a well-established association between fluid retention and weight gain with mortality in ARDS,4,28,30 –32 little is known about the physiologic effects of intravascular volume reduction in these patients. Retrospective analyses suggest improved survival with temporal decrements in hydrostatic pressures,31 with negative fluid balance being a strong predictor of survival in a broader group of critically ill patients.33 A prospective trial CHEST / 122 / 6 / DECEMBER, 2002
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randomizing patients with pulmonary edema to a fluid-restrictive strategy found reductions in duration of mechanical ventilation and ICU stay.34 Given that 82% of patients with ALI may manifest increased hydrostatic pressures at least intermittently, using the VPW as an aid in monitoring fluid balance may be immediately clinically applicable.35 From the current data, we conclude that readily available radiographic measures are representative of changes in intravascular volume in critically ill patients. Furthermore, objective radiographic measurements of the VPW may be a better indicator of volume status than more frequently used traditional subjective measurements (eg, quadrant counting or edema grading), which did not change significantly in this investigation despite marked shifts in fluid balance. Importantly, diuresis with resultant weight loss is radiographically evident in patients with ALI through reductions in VPW. These data suggest that roughly half of the changes in fluid balance or weight in patients with ALI treated with colloids and diuretics are detected radiographically by changes in VPW. However, it must be emphasized that intake/output and body weight may vary substantially without obvious cause. Great care was taken in this study to capture all measurable changes in fluid balance and body weight, thus allowing at least moderate correlations between body weight, net fluid balance, and VPW. Despite strict attention to such data, a substantial disparity exists between fluid balance and weight change.36 The most logical explanation for this is the difficulty in quantifying insensible fluid losses in critically ill patients, thus promoting weight as the simpler and more accurate fluid balance variable. In standard clinical settings where fluid balance parameters are tracked much less rigorously, sequential evaluation of the VPW could allow for easier and more reproducible determination of changes in intravascular volume. This is supported by the high interrater and intrarater correlation coefficients for measuring VPW.15,16 The relevance of these findings relates to the difficulty in determining intravascular volume in critically ill patients1–3 and the ready availability of radiographs in ICU patients. The majority of CXRs obtained from ICU patients receiving mechanical ventilation result in a change in therapy (66%), with the most frequent intervention being institution of diuretic therapy.37 This attests to the fact that physicians commonly incorporate CXR findings into management decisions regarding volume status, perhaps without fully understanding or maximizing their interpretation. For example, the accuracy of radiographically differentiating hydrostatic from permeability pulmonary edema is improved from 41 to 70% with the inclusion of VPW and CTR.15,16 Combining 2092
data from other modalities in the assessment of intravascular volume may be necessary. The majority of strategies designed to assess intravascular volume have shown limited success or resulted in substantial increases in resource utilization from other diagnostic modalities.18,38 Yet, these diagnostic algorithms have generally failed to incorporate readily available complementary information available from CXRs, such as the VPW. These data establish that CXRs are similarly sensitive to changes in invasive estimates of intravascular volume (accounting for 49% of changes in PAOP). This relationship is less well defined for CVP, which is less accurate for determination of cardiac preload or intravascular volume. As with discrepancies between fluid balance and body weight changes, intravascular volume may be affected by external variables, such as plasma COP or capillary permeability, which may continuously affect intravascular volume. Invasive measurements available from pulmonary artery catheterization provide pressure measures from which volume may be extrapolated (eg, PAOP as a measure of left ventricular end-diastolic volume). These pressure measures are influenced substantially by changes in cardiac compliance and contractility as well as intrathoracic pressure, and thus do not solely portray changes in intravascular volume. These data suggest that the known correlation of VPW with intravascular volume in upright radiographs12,14,18 may be extended to the standard radiographs available in the ICU. Serial CXRs may thus serve as a readily available clinical tool from which to extrapolate intravascular volume information regardless of interposed variables that complicate assumptions of intravascular volume from PAC measures. For these reasons, significant weight may be attached to the VPW as a measure of intravascular volume status, supporting its use in a clinical decision model complementing traditional information, such as fluid balance, physical examination, and laboratory studies. Limitations of this investigation include the uniformity of the patient population enrolled into this investigation (ie, ALI/ARDS patients) and the use of a single radiologist for interpretation of CXRs. Spectrum bias, the enhanced sensitivity of a test for the patient population in which it was derived, would mandate that our findings be reproduced in patients without ALI/ARDS.39 The ability to discriminate VPW may be affected by parenchymal lung densities (such as in ALI),40 making this measure potentially even more useful in mechanically ventilated patients as a whole. VPW is the most sensitive noninvasive indicator of intravascular volume, as it reflects both venous (right-sided) and arterial (left-sided) structures.41 Pistolesi and colleagues12 reported that volClinical Investigations in Critical Care
ume expansion of 1.0 L resulted in widening of the VPW by 5.0 mm in erect CXRs. Though radiographically detectable, the difference noted in this population with supine, portable CXRs was less marked (ie, a 5.0-mm VPW reduction corresponded to a 3.2-L negative fluid balance), possibly due to differences in technique or overlying parenchymal densities associated with ALI. In the era of digital radiography, computerized digital calipers could allow for more accurate measures, making small reductions in VPW more readily detectable. Fifteen degrees of left anterior oblique projection may reduce VPW by 6%,24 and thus implementation of standardized radiographic techniques is important to maximize CXR interpretation, as shown by improvements in interpretative accuracy with adaptive training.42,43 Consistency of technique is apparent in Figure 3, where the degree of left anterior oblique rotation is equal between radiographs. We chose to use the PAC to assess intravascular volume because of its acceptance as the clinical “gold standard.” Despite its broad use, the inherent limitations of the PAC for hemodynamic monitoring must be noted, particularly as it relates to preload assessment. Often used for such information, the potential discrepancies in estimating vascular volumes from PAC pressure measurements must be acknowledged, as described previously. Interpreting these data, therefore, requires that clinicians recognize the potential inaccuracies in estimating intravascular volume from PAC measures. It should also be considered that all barometric measures (ie, those available from PAC) do not account for volumetric changes attributable to changes in COP. Intravascu-
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lar volume rises in tandem with increases in COP, at least partially independent of hydrostatic pressure, and thus the PAC does not specifically account for changes in COP. As such, given the changes in serum protein concentrations, true intravascular volume may have changed more or less than predicted by PAOP. In conclusion, this study provides previously unrecognized information about sequential changes in radiographic appearance during fluid balance manipulations. We have shown that objective radiographic measurement of the VPW from portable, supine CXRs, which are universally available in ICU patients, correlates highly with bedside measures of fluid balance and invasive estimates of intravascular volume. Considering the risks associated with invasive monitoring strategies and the growing complexity of algorithms including novel diagnostic modalities, refining current methods of monitoring volume status in our most critically ill patients is imperative. If confirmed in a prospective data set of a varied ICU patient population, these findings may advance the training of both radiologists and intensivists, who are currently taught little regarding objective vascular measures, such as the VPW. Exploitation of available CXR data may lead to reductions in procedurerelated adverse events and thus may improve patient outcomes without additional resource utilization, and should be tested in prospective clinical trials. ACKNOWLEDGMENT: The authors thank Linda Collins, RN, Susan Bozeman, RN, and our ICU patients and families. We also thank Drew Imhulse at Emory University for technical and artistic assistance.
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Appendix
*MR ⫽ medical record; CT ⫽ cardiothoracic; NL ⫽ normal; SVC ⫽ superior vena cava; RUQ ⫽ right upper quadrant; RLQ ⫽ right lower quadrant; LUQ ⫽ left upper quadrant; LLQ ⫽ left lower quadrant.
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