Ultrasound Measurement to Estimate CVP

Severe sepsis and septic shock account for more than 750,000 hospital admissions and 215,000 deaths per year.1 Early fluid resuscitation is the cornerstone of treatment, and early goal‐directed therapy (EGDT), which includes a target central venous pressure (CVP) of 8 to 12 mm Hg, has been shown to improve outcomes, including mortality and length of stay.2 This goal allows appropriate initial resuscitation and may decrease the risk of excess fluid administration, which is related to adverse outcomes in critically ill patients.3 However, nonintensivists may not start early aggressive fluid resuscitation because of inability to accurately assess intravascular volume, concerns for inadvertent volume overload, or the difficulty of recognizing insidious illness. Assessment of volume status, primarily from inspection of the internal jugular vein to estimate CVP, is difficult to perform by clinical examination alone, especially if CVP is very low.4 Inspection of the external jugular vein is perhaps easier than inspecting the internal jugular vein and appears to accurately estimate CVP,5 but it does not allow the degree of precision necessary for EGDT. Echocardiography can estimate CVP based on respirophasic variation or collapsibility index, but this technique requires expensive equipment and sonographic expertise. The current gold standard technique for measuring CVP requires an invasive central venous catheter, which can delay timely resuscitation and is associated with complications.6

An alternative technique to guide resuscitation efforts should be accurate, safe, rapid, and easy to perform at the bedside, while providing real‐time measurement results. We hypothesized that CVP can be accurately assessed using noninvasive ultrasound imaging of the internal jugular vein, since jugular venous pressure is essentially equal to CVP.7 Specifically, our study estimated the diagnostic accuracy of ultrasound measurement of the aspect ratio (height/width) of the internal jugular vein compared with the invasively measured CVP target for EGDT. We expected that a lower aspect ratio would correlate with a lower CVP and a higher aspect ratio would correlate with a higher CVP.

Methods

Volunteers were enrolled at Saint Mary's Hospital (Mayo Clinic) in Rochester, MN, from January to March 2006, and patients were enrolled at Saint Mary's Hospital and at Abbott Northwestern Hospital (Allina Hospitals and Clinics) in Minneapolis, MN, from May 2006 to October 2007. The study was approved by the Institutional Review Boards of Mayo Clinic and Allina and had 2 phases. The first phase comprised ultrasound measurements of internal jugular vein aspect ratio and determination of intraobserver and interobserver agreement in healthy volunteers. The second phase involved measurement of internal jugular vein aspect ratio and invasive CVP in a convenience sample of 44 spontaneously breathing patients admitted to medical intensive care units: 9 patients at Saint Marys Hospital and 35 patients at Abbott Northwestern Hospital. Patients were enrolled only when study members were on duty in the intensive care unit and able to perform study measurements. As a result, a high proportion of patients who may have been eligible were not asked to participate.

Each volunteer was deemed euvolemic on the basis of normal orthostatic measurements and normal oral intake with no vomiting or diarrhea in the previous 5 days. Measurements of 19 volunteers were made by 1 author (A.S.K.), with subsequent measurements of 15 of the volunteers made by another author (O.G.) to determine interobserver variability; 4 participants did not undergo a second measurement because of scheduling conflicts.

Inclusion and exclusion criteria for the critically ill patients are provided in Table 1. Recruitment was based on presenting symptoms and test results that led the intensive care unit physicians to decide to place a CVP monitor. All the enrolled patients had invasive CVP measurement performed approximately 30 to 40 minutes after ultrasound measurement of the internal jugular vein; this delay was the time required to place the central line and obtain the measurement. All patients who were invited to participate in the study were included. No patients were excluded on the basis of the exclusion criteria or because of inability to place a central line. No complications related to central line placement occurred.

We followed a prescribed measurement technique (Table 2) to determine the internal jugular vein aspect ratio in all volunteers and patients. Measurements of the volunteers were made with a Site‐Rite 3 Ultrasound System (Bard Access Systems, Inc., Salt Lake City, UT) using a 9.0‐MHz transducer. Measurements of the critically ill patients were made with a SonoSite MicroMaxx ultrasound system (SonoSite, Inc., Bothell, WA) using a 10.5‐MHz transducer. Study team physicians initially were blinded to actual measured CVP. Internal jugular vein aspect ratio and CVP were measured at tidal volume end‐expiration for all patients. One measurement was obtained for each patient, with measurements being made by 1 of 4 physicians (2 intensivists, 1 critical care fellow, and 1 chief medicine resident). With no specific ultrasound training and with only minimal practice, the physicians could obtain the optimal aspect ratio within a few seconds (Figure 1).

Figure 1

This was an exploratory prospective study, and all methods of data collection were designed before patient enrollment. However, the ultrasound‐derived aspect ratio of 0.83 (which defined a CVP of 8 mm Hg) was determined post hoc to maximize sensitivity and specificity and was based on the aspect ratio of the euvolemic volunteers and the inflection point of the CVP vs aspect ratio curve for the critically ill patients.

Results

We first evaluated 19 white volunteers: 12 women and 7 men. Mean (SD) age was 42 (11) years and mean body mass index was 26.6 (4.5) kg/m². Mean arterial pressure was 89 (13) mm Hg and mean heart rate was 71 (15) beats/minute. Mean aspect ratio of the right and left internal jugular vein for all volunteers was 0.82 (0.07). There was no difference in aspect ratio between the right (0.83 [0.10]) and left (0.81 [0.13]) vein (P > 0.10). Also, no difference in the aspect ratio was seen between men (0.81 [0.08]) and women (0.83 [0.07]) (P = 0.77). Bland‐Altman analysis indicated moderate intraobserver and interobserver agreement for the aspect ratio measurements (Figure 2).

Figure 2

We then compared the aspect ratio measured using ultrasound and CVP measured with an invasive monitor for 44 spontaneously breathing critically ill patients (22 women and 22 men; 38 were white). Mean (SD) age was 66 (14) years and mean body mass index was 28.8 (9.1) kg/m². Mean arterial pressure (n = 36) was 67 (12) mm Hg and mean heart rate (n = 34) was 92 (22) beats/minute. Systemic inflammatory response syndrome (SIRS) criteria were present in 23 of 40 patients; complete data were unavailable for the other 4 patients. Of these 40 patients, 20 had sepsis, 15 had severe sepsis, and 5 had septic shock. The most common diagnoses were gastrointestinal tract bleeding in 6 patients and congestive heart failure in 4 patients. Acute Physiology and Chronic Health Evaluation (APACHE III) score, available for 8 of the 9 patients at Saint Marys Hospital, was 63 (10).

Figure 3 shows measured aspect ratios vs. invasively measured CVP for the critically ill patients. The curvilinear result is consistent with venous and right ventricular compliance ( volume/ pressure) characteristics. Note that the inflection point (beginning of the increased slope) of the curve corresponds to a CVP of about 8 mm Hg. Furthermore, the aspect ratio (0.8) at this point is the same as that seen in the euvolemic volunteers. These findings suggest that, in spontaneously breathing patients, a CVP of about 8 mm Hg and an aspect ratio of about 0.8 each defines the beginning of the plateau on the cardiac Frank‐Starling curve.

Figure 3

Ultrasound imaging of the internal jugular vein aspect ratio accurately estimated the CVP target of 8 mm Hg based on the area under the receiver operating characteristics curve of 0.84 (95% confidence interval [CI], 0.72‐0.96) (Figure 4). For an invasively measured CVP of less than 8 mm Hg, the likelihood ratio for a positive ultrasound test result (aspect ratio < 0.83) was 3.5 (95% CI, 1.4‐8.4) and for a negative test result (aspect ratio 0.83) was 0.30 (95% CI, 0.14‐0.62). Clinically, this means that patients with a measured aspect ratio of less than 0.83 require further fluid resuscitation, whereas patients with a measured aspect ratio of 0.83 or greater are less likely to benefit from fluid resuscitation.

Figure 4

Discussion

This study demonstrated that the EGDT CVP target of 8 to 12 mm Hg can be accurately estimated (referenced to invasive CVP monitoring) using noninvasive ultrasound measurement of the internal jugular vein in spontaneously breathing critically ill patients. The measurement process is simple to perform at the bedside and moderately reliable when performed by different observers; also, the results appear to be equivalent for both sides and for males or females. Images can be stored electronically for serial comparisons and for viewing by other caregivers. Because the aspect ratio is essentially constant over the length of the internal jugular vein, unlike diameter, measurements can be performed anywhere along the vein. Also, ultrasound imaging allows visualization of the internal jugular vein despite anatomic variation.9

Previous attempts at noninvasive hemodynamic monitoring using plethysmography, thoracic electrical bioimpedance, and external Doppler probes have shown these methods to be cumbersome or inaccurate.1013 Other investigators have used echocardiography14, 15 and handheld ultrasound16 to image the diameter of the inferior vena cava in order to assess intravascular volume status, but these techniques require expertise in sonographic imaging. An alternative technique is to measure peripheral venous pressure, which correlates with CVP.17 This method, however, requires technical expertise to zero the monitor and is not yet widely used for critically ill patients. A literature search found 1 letter to the editor suggesting that real‐time ultrasound imaging of the internal jugular vein could be used to qualitatively determine jugular venous pressure18 and 3 studies using ultrasound in conjunction with a pressure transducer or manometer to determine the pressure needed to collapse the vein (either the internal jugular or a peripheral vein), with subsequent correlation to CVP.1921 These latter techniques appear to be cumbersome and require custom equipment that is not readily available in most hospitals.

Any measurement of CVP, including our technique, assumes correlation with volume responsiveness as a surrogate for intravascular volume. However, CVP is governed by multiple physiologic and pathologic factors, including intravascular volume, vascular and ventricular compliance, ventricular function, tricuspid stenosis and regurgitation, cardiac tamponade, and atrioventricular dissociation.22, 23 Therefore, CVP alone may not be an accurate measure of volume responsiveness (intravascular volume). CVP may also have spontaneous variation similar to pulmonary capillary wedge pressure, which can be as high as 7 mm Hg in any given patient.24 Furthermore, invasive CVP monitors also have limitations, and the overall accuracy of the Philips system used at Saint Marys Hospital is 4% of the reading or 4 mm Hg, whichever is greater.25 Nonetheless, the EGDT algorithm that incorporates CVP measurement with a target of 8 to 12 mm Hg in spontaneously breathing patients and 12 mm Hg in mechanically ventilated patients has resulted in decreased mortality among patients with severe sepsis and is recommended by the Surviving Sepsis Campaign guidelines26 and the Institute for Healthcare Improvement.27

These study results are important because nonintensivists such as hospitalists and emergency department physicians can use this technique to provide rapid fluid resuscitation early in the course of severe sepsis and septic shock, when aggressive fluid resuscitation is most effective. Ultrasound imaging of the internal jugular vein is easy to perform without formal training, and the equipment is readily available in most hospitals. Future studies will evaluate outcomes in spontaneously breathing and ventilated patients to determine the accuracy of this measurement technique in volume‐depleted and volume‐overloaded states. If validated in different patient populations, ultrasound measurement of the internal jugular vein could substitute for the EGDT CVP target in critically ill patients and allow early aggressive fluid resuscitation before a central venous catheter is placed.

Severe sepsis and septic shock account for more than 750,000 hospital admissions and 215,000 deaths per year.1 Early fluid resuscitation is the cornerstone of treatment, and early goal‐directed therapy (EGDT), which includes a target central venous pressure (CVP) of 8 to 12 mm Hg, has been shown to improve outcomes, including mortality and length of stay.2 This goal allows appropriate initial resuscitation and may decrease the risk of excess fluid administration, which is related to adverse outcomes in critically ill patients.3 However, nonintensivists may not start early aggressive fluid resuscitation because of inability to accurately assess intravascular volume, concerns for inadvertent volume overload, or the difficulty of recognizing insidious illness. Assessment of volume status, primarily from inspection of the internal jugular vein to estimate CVP, is difficult to perform by clinical examination alone, especially if CVP is very low.4 Inspection of the external jugular vein is perhaps easier than inspecting the internal jugular vein and appears to accurately estimate CVP,5 but it does not allow the degree of precision necessary for EGDT. Echocardiography can estimate CVP based on respirophasic variation or collapsibility index, but this technique requires expensive equipment and sonographic expertise. The current gold standard technique for measuring CVP requires an invasive central venous catheter, which can delay timely resuscitation and is associated with complications.6

An alternative technique to guide resuscitation efforts should be accurate, safe, rapid, and easy to perform at the bedside, while providing real‐time measurement results. We hypothesized that CVP can be accurately assessed using noninvasive ultrasound imaging of the internal jugular vein, since jugular venous pressure is essentially equal to CVP.7 Specifically, our study estimated the diagnostic accuracy of ultrasound measurement of the aspect ratio (height/width) of the internal jugular vein compared with the invasively measured CVP target for EGDT. We expected that a lower aspect ratio would correlate with a lower CVP and a higher aspect ratio would correlate with a higher CVP.

Methods

Volunteers were enrolled at Saint Mary's Hospital (Mayo Clinic) in Rochester, MN, from January to March 2006, and patients were enrolled at Saint Mary's Hospital and at Abbott Northwestern Hospital (Allina Hospitals and Clinics) in Minneapolis, MN, from May 2006 to October 2007. The study was approved by the Institutional Review Boards of Mayo Clinic and Allina and had 2 phases. The first phase comprised ultrasound measurements of internal jugular vein aspect ratio and determination of intraobserver and interobserver agreement in healthy volunteers. The second phase involved measurement of internal jugular vein aspect ratio and invasive CVP in a convenience sample of 44 spontaneously breathing patients admitted to medical intensive care units: 9 patients at Saint Marys Hospital and 35 patients at Abbott Northwestern Hospital. Patients were enrolled only when study members were on duty in the intensive care unit and able to perform study measurements. As a result, a high proportion of patients who may have been eligible were not asked to participate.

Each volunteer was deemed euvolemic on the basis of normal orthostatic measurements and normal oral intake with no vomiting or diarrhea in the previous 5 days. Measurements of 19 volunteers were made by 1 author (A.S.K.), with subsequent measurements of 15 of the volunteers made by another author (O.G.) to determine interobserver variability; 4 participants did not undergo a second measurement because of scheduling conflicts.

Inclusion and exclusion criteria for the critically ill patients are provided in Table 1. Recruitment was based on presenting symptoms and test results that led the intensive care unit physicians to decide to place a CVP monitor. All the enrolled patients had invasive CVP measurement performed approximately 30 to 40 minutes after ultrasound measurement of the internal jugular vein; this delay was the time required to place the central line and obtain the measurement. All patients who were invited to participate in the study were included. No patients were excluded on the basis of the exclusion criteria or because of inability to place a central line. No complications related to central line placement occurred.

We followed a prescribed measurement technique (Table 2) to determine the internal jugular vein aspect ratio in all volunteers and patients. Measurements of the volunteers were made with a Site‐Rite 3 Ultrasound System (Bard Access Systems, Inc., Salt Lake City, UT) using a 9.0‐MHz transducer. Measurements of the critically ill patients were made with a SonoSite MicroMaxx ultrasound system (SonoSite, Inc., Bothell, WA) using a 10.5‐MHz transducer. Study team physicians initially were blinded to actual measured CVP. Internal jugular vein aspect ratio and CVP were measured at tidal volume end‐expiration for all patients. One measurement was obtained for each patient, with measurements being made by 1 of 4 physicians (2 intensivists, 1 critical care fellow, and 1 chief medicine resident). With no specific ultrasound training and with only minimal practice, the physicians could obtain the optimal aspect ratio within a few seconds (Figure 1).

Figure 1

This was an exploratory prospective study, and all methods of data collection were designed before patient enrollment. However, the ultrasound‐derived aspect ratio of 0.83 (which defined a CVP of 8 mm Hg) was determined post hoc to maximize sensitivity and specificity and was based on the aspect ratio of the euvolemic volunteers and the inflection point of the CVP vs aspect ratio curve for the critically ill patients.

Results

We first evaluated 19 white volunteers: 12 women and 7 men. Mean (SD) age was 42 (11) years and mean body mass index was 26.6 (4.5) kg/m². Mean arterial pressure was 89 (13) mm Hg and mean heart rate was 71 (15) beats/minute. Mean aspect ratio of the right and left internal jugular vein for all volunteers was 0.82 (0.07). There was no difference in aspect ratio between the right (0.83 [0.10]) and left (0.81 [0.13]) vein (P > 0.10). Also, no difference in the aspect ratio was seen between men (0.81 [0.08]) and women (0.83 [0.07]) (P = 0.77). Bland‐Altman analysis indicated moderate intraobserver and interobserver agreement for the aspect ratio measurements (Figure 2).

Figure 2

We then compared the aspect ratio measured using ultrasound and CVP measured with an invasive monitor for 44 spontaneously breathing critically ill patients (22 women and 22 men; 38 were white). Mean (SD) age was 66 (14) years and mean body mass index was 28.8 (9.1) kg/m². Mean arterial pressure (n = 36) was 67 (12) mm Hg and mean heart rate (n = 34) was 92 (22) beats/minute. Systemic inflammatory response syndrome (SIRS) criteria were present in 23 of 40 patients; complete data were unavailable for the other 4 patients. Of these 40 patients, 20 had sepsis, 15 had severe sepsis, and 5 had septic shock. The most common diagnoses were gastrointestinal tract bleeding in 6 patients and congestive heart failure in 4 patients. Acute Physiology and Chronic Health Evaluation (APACHE III) score, available for 8 of the 9 patients at Saint Marys Hospital, was 63 (10).

Figure 3 shows measured aspect ratios vs. invasively measured CVP for the critically ill patients. The curvilinear result is consistent with venous and right ventricular compliance ( volume/ pressure) characteristics. Note that the inflection point (beginning of the increased slope) of the curve corresponds to a CVP of about 8 mm Hg. Furthermore, the aspect ratio (0.8) at this point is the same as that seen in the euvolemic volunteers. These findings suggest that, in spontaneously breathing patients, a CVP of about 8 mm Hg and an aspect ratio of about 0.8 each defines the beginning of the plateau on the cardiac Frank‐Starling curve.

Figure 3

Ultrasound imaging of the internal jugular vein aspect ratio accurately estimated the CVP target of 8 mm Hg based on the area under the receiver operating characteristics curve of 0.84 (95% confidence interval [CI], 0.72‐0.96) (Figure 4). For an invasively measured CVP of less than 8 mm Hg, the likelihood ratio for a positive ultrasound test result (aspect ratio < 0.83) was 3.5 (95% CI, 1.4‐8.4) and for a negative test result (aspect ratio 0.83) was 0.30 (95% CI, 0.14‐0.62). Clinically, this means that patients with a measured aspect ratio of less than 0.83 require further fluid resuscitation, whereas patients with a measured aspect ratio of 0.83 or greater are less likely to benefit from fluid resuscitation.

Figure 4

Discussion

This study demonstrated that the EGDT CVP target of 8 to 12 mm Hg can be accurately estimated (referenced to invasive CVP monitoring) using noninvasive ultrasound measurement of the internal jugular vein in spontaneously breathing critically ill patients. The measurement process is simple to perform at the bedside and moderately reliable when performed by different observers; also, the results appear to be equivalent for both sides and for males or females. Images can be stored electronically for serial comparisons and for viewing by other caregivers. Because the aspect ratio is essentially constant over the length of the internal jugular vein, unlike diameter, measurements can be performed anywhere along the vein. Also, ultrasound imaging allows visualization of the internal jugular vein despite anatomic variation.9

Previous attempts at noninvasive hemodynamic monitoring using plethysmography, thoracic electrical bioimpedance, and external Doppler probes have shown these methods to be cumbersome or inaccurate.1013 Other investigators have used echocardiography14, 15 and handheld ultrasound16 to image the diameter of the inferior vena cava in order to assess intravascular volume status, but these techniques require expertise in sonographic imaging. An alternative technique is to measure peripheral venous pressure, which correlates with CVP.17 This method, however, requires technical expertise to zero the monitor and is not yet widely used for critically ill patients. A literature search found 1 letter to the editor suggesting that real‐time ultrasound imaging of the internal jugular vein could be used to qualitatively determine jugular venous pressure18 and 3 studies using ultrasound in conjunction with a pressure transducer or manometer to determine the pressure needed to collapse the vein (either the internal jugular or a peripheral vein), with subsequent correlation to CVP.1921 These latter techniques appear to be cumbersome and require custom equipment that is not readily available in most hospitals.

Any measurement of CVP, including our technique, assumes correlation with volume responsiveness as a surrogate for intravascular volume. However, CVP is governed by multiple physiologic and pathologic factors, including intravascular volume, vascular and ventricular compliance, ventricular function, tricuspid stenosis and regurgitation, cardiac tamponade, and atrioventricular dissociation.22, 23 Therefore, CVP alone may not be an accurate measure of volume responsiveness (intravascular volume). CVP may also have spontaneous variation similar to pulmonary capillary wedge pressure, which can be as high as 7 mm Hg in any given patient.24 Furthermore, invasive CVP monitors also have limitations, and the overall accuracy of the Philips system used at Saint Marys Hospital is 4% of the reading or 4 mm Hg, whichever is greater.25 Nonetheless, the EGDT algorithm that incorporates CVP measurement with a target of 8 to 12 mm Hg in spontaneously breathing patients and 12 mm Hg in mechanically ventilated patients has resulted in decreased mortality among patients with severe sepsis and is recommended by the Surviving Sepsis Campaign guidelines26 and the Institute for Healthcare Improvement.27

These study results are important because nonintensivists such as hospitalists and emergency department physicians can use this technique to provide rapid fluid resuscitation early in the course of severe sepsis and septic shock, when aggressive fluid resuscitation is most effective. Ultrasound imaging of the internal jugular vein is easy to perform without formal training, and the equipment is readily available in most hospitals. Future studies will evaluate outcomes in spontaneously breathing and ventilated patients to determine the accuracy of this measurement technique in volume‐depleted and volume‐overloaded states. If validated in different patient populations, ultrasound measurement of the internal jugular vein could substitute for the EGDT CVP target in critically ill patients and allow early aggressive fluid resuscitation before a central venous catheter is placed.

Severe sepsis and septic shock account for more than 750,000 hospital admissions and 215,000 deaths per year.1 Early fluid resuscitation is the cornerstone of treatment, and early goal‐directed therapy (EGDT), which includes a target central venous pressure (CVP) of 8 to 12 mm Hg, has been shown to improve outcomes, including mortality and length of stay.2 This goal allows appropriate initial resuscitation and may decrease the risk of excess fluid administration, which is related to adverse outcomes in critically ill patients.3 However, nonintensivists may not start early aggressive fluid resuscitation because of inability to accurately assess intravascular volume, concerns for inadvertent volume overload, or the difficulty of recognizing insidious illness. Assessment of volume status, primarily from inspection of the internal jugular vein to estimate CVP, is difficult to perform by clinical examination alone, especially if CVP is very low.4 Inspection of the external jugular vein is perhaps easier than inspecting the internal jugular vein and appears to accurately estimate CVP,5 but it does not allow the degree of precision necessary for EGDT. Echocardiography can estimate CVP based on respirophasic variation or collapsibility index, but this technique requires expensive equipment and sonographic expertise. The current gold standard technique for measuring CVP requires an invasive central venous catheter, which can delay timely resuscitation and is associated with complications.6

An alternative technique to guide resuscitation efforts should be accurate, safe, rapid, and easy to perform at the bedside, while providing real‐time measurement results. We hypothesized that CVP can be accurately assessed using noninvasive ultrasound imaging of the internal jugular vein, since jugular venous pressure is essentially equal to CVP.7 Specifically, our study estimated the diagnostic accuracy of ultrasound measurement of the aspect ratio (height/width) of the internal jugular vein compared with the invasively measured CVP target for EGDT. We expected that a lower aspect ratio would correlate with a lower CVP and a higher aspect ratio would correlate with a higher CVP.

Methods

Volunteers were enrolled at Saint Mary's Hospital (Mayo Clinic) in Rochester, MN, from January to March 2006, and patients were enrolled at Saint Mary's Hospital and at Abbott Northwestern Hospital (Allina Hospitals and Clinics) in Minneapolis, MN, from May 2006 to October 2007. The study was approved by the Institutional Review Boards of Mayo Clinic and Allina and had 2 phases. The first phase comprised ultrasound measurements of internal jugular vein aspect ratio and determination of intraobserver and interobserver agreement in healthy volunteers. The second phase involved measurement of internal jugular vein aspect ratio and invasive CVP in a convenience sample of 44 spontaneously breathing patients admitted to medical intensive care units: 9 patients at Saint Marys Hospital and 35 patients at Abbott Northwestern Hospital. Patients were enrolled only when study members were on duty in the intensive care unit and able to perform study measurements. As a result, a high proportion of patients who may have been eligible were not asked to participate.

Each volunteer was deemed euvolemic on the basis of normal orthostatic measurements and normal oral intake with no vomiting or diarrhea in the previous 5 days. Measurements of 19 volunteers were made by 1 author (A.S.K.), with subsequent measurements of 15 of the volunteers made by another author (O.G.) to determine interobserver variability; 4 participants did not undergo a second measurement because of scheduling conflicts.

Inclusion and exclusion criteria for the critically ill patients are provided in Table 1. Recruitment was based on presenting symptoms and test results that led the intensive care unit physicians to decide to place a CVP monitor. All the enrolled patients had invasive CVP measurement performed approximately 30 to 40 minutes after ultrasound measurement of the internal jugular vein; this delay was the time required to place the central line and obtain the measurement. All patients who were invited to participate in the study were included. No patients were excluded on the basis of the exclusion criteria or because of inability to place a central line. No complications related to central line placement occurred.

We followed a prescribed measurement technique (Table 2) to determine the internal jugular vein aspect ratio in all volunteers and patients. Measurements of the volunteers were made with a Site‐Rite 3 Ultrasound System (Bard Access Systems, Inc., Salt Lake City, UT) using a 9.0‐MHz transducer. Measurements of the critically ill patients were made with a SonoSite MicroMaxx ultrasound system (SonoSite, Inc., Bothell, WA) using a 10.5‐MHz transducer. Study team physicians initially were blinded to actual measured CVP. Internal jugular vein aspect ratio and CVP were measured at tidal volume end‐expiration for all patients. One measurement was obtained for each patient, with measurements being made by 1 of 4 physicians (2 intensivists, 1 critical care fellow, and 1 chief medicine resident). With no specific ultrasound training and with only minimal practice, the physicians could obtain the optimal aspect ratio within a few seconds (Figure 1).

Figure 1

This was an exploratory prospective study, and all methods of data collection were designed before patient enrollment. However, the ultrasound‐derived aspect ratio of 0.83 (which defined a CVP of 8 mm Hg) was determined post hoc to maximize sensitivity and specificity and was based on the aspect ratio of the euvolemic volunteers and the inflection point of the CVP vs aspect ratio curve for the critically ill patients.

Results

We first evaluated 19 white volunteers: 12 women and 7 men. Mean (SD) age was 42 (11) years and mean body mass index was 26.6 (4.5) kg/m². Mean arterial pressure was 89 (13) mm Hg and mean heart rate was 71 (15) beats/minute. Mean aspect ratio of the right and left internal jugular vein for all volunteers was 0.82 (0.07). There was no difference in aspect ratio between the right (0.83 [0.10]) and left (0.81 [0.13]) vein (P > 0.10). Also, no difference in the aspect ratio was seen between men (0.81 [0.08]) and women (0.83 [0.07]) (P = 0.77). Bland‐Altman analysis indicated moderate intraobserver and interobserver agreement for the aspect ratio measurements (Figure 2).

Figure 2

We then compared the aspect ratio measured using ultrasound and CVP measured with an invasive monitor for 44 spontaneously breathing critically ill patients (22 women and 22 men; 38 were white). Mean (SD) age was 66 (14) years and mean body mass index was 28.8 (9.1) kg/m². Mean arterial pressure (n = 36) was 67 (12) mm Hg and mean heart rate (n = 34) was 92 (22) beats/minute. Systemic inflammatory response syndrome (SIRS) criteria were present in 23 of 40 patients; complete data were unavailable for the other 4 patients. Of these 40 patients, 20 had sepsis, 15 had severe sepsis, and 5 had septic shock. The most common diagnoses were gastrointestinal tract bleeding in 6 patients and congestive heart failure in 4 patients. Acute Physiology and Chronic Health Evaluation (APACHE III) score, available for 8 of the 9 patients at Saint Marys Hospital, was 63 (10).

Figure 3 shows measured aspect ratios vs. invasively measured CVP for the critically ill patients. The curvilinear result is consistent with venous and right ventricular compliance ( volume/ pressure) characteristics. Note that the inflection point (beginning of the increased slope) of the curve corresponds to a CVP of about 8 mm Hg. Furthermore, the aspect ratio (0.8) at this point is the same as that seen in the euvolemic volunteers. These findings suggest that, in spontaneously breathing patients, a CVP of about 8 mm Hg and an aspect ratio of about 0.8 each defines the beginning of the plateau on the cardiac Frank‐Starling curve.

Figure 3

Ultrasound imaging of the internal jugular vein aspect ratio accurately estimated the CVP target of 8 mm Hg based on the area under the receiver operating characteristics curve of 0.84 (95% confidence interval [CI], 0.72‐0.96) (Figure 4). For an invasively measured CVP of less than 8 mm Hg, the likelihood ratio for a positive ultrasound test result (aspect ratio < 0.83) was 3.5 (95% CI, 1.4‐8.4) and for a negative test result (aspect ratio 0.83) was 0.30 (95% CI, 0.14‐0.62). Clinically, this means that patients with a measured aspect ratio of less than 0.83 require further fluid resuscitation, whereas patients with a measured aspect ratio of 0.83 or greater are less likely to benefit from fluid resuscitation.

Figure 4

Discussion

This study demonstrated that the EGDT CVP target of 8 to 12 mm Hg can be accurately estimated (referenced to invasive CVP monitoring) using noninvasive ultrasound measurement of the internal jugular vein in spontaneously breathing critically ill patients. The measurement process is simple to perform at the bedside and moderately reliable when performed by different observers; also, the results appear to be equivalent for both sides and for males or females. Images can be stored electronically for serial comparisons and for viewing by other caregivers. Because the aspect ratio is essentially constant over the length of the internal jugular vein, unlike diameter, measurements can be performed anywhere along the vein. Also, ultrasound imaging allows visualization of the internal jugular vein despite anatomic variation.9

Previous attempts at noninvasive hemodynamic monitoring using plethysmography, thoracic electrical bioimpedance, and external Doppler probes have shown these methods to be cumbersome or inaccurate.1013 Other investigators have used echocardiography14, 15 and handheld ultrasound16 to image the diameter of the inferior vena cava in order to assess intravascular volume status, but these techniques require expertise in sonographic imaging. An alternative technique is to measure peripheral venous pressure, which correlates with CVP.17 This method, however, requires technical expertise to zero the monitor and is not yet widely used for critically ill patients. A literature search found 1 letter to the editor suggesting that real‐time ultrasound imaging of the internal jugular vein could be used to qualitatively determine jugular venous pressure18 and 3 studies using ultrasound in conjunction with a pressure transducer or manometer to determine the pressure needed to collapse the vein (either the internal jugular or a peripheral vein), with subsequent correlation to CVP.1921 These latter techniques appear to be cumbersome and require custom equipment that is not readily available in most hospitals.

Any measurement of CVP, including our technique, assumes correlation with volume responsiveness as a surrogate for intravascular volume. However, CVP is governed by multiple physiologic and pathologic factors, including intravascular volume, vascular and ventricular compliance, ventricular function, tricuspid stenosis and regurgitation, cardiac tamponade, and atrioventricular dissociation.22, 23 Therefore, CVP alone may not be an accurate measure of volume responsiveness (intravascular volume). CVP may also have spontaneous variation similar to pulmonary capillary wedge pressure, which can be as high as 7 mm Hg in any given patient.24 Furthermore, invasive CVP monitors also have limitations, and the overall accuracy of the Philips system used at Saint Marys Hospital is 4% of the reading or 4 mm Hg, whichever is greater.25 Nonetheless, the EGDT algorithm that incorporates CVP measurement with a target of 8 to 12 mm Hg in spontaneously breathing patients and 12 mm Hg in mechanically ventilated patients has resulted in decreased mortality among patients with severe sepsis and is recommended by the Surviving Sepsis Campaign guidelines26 and the Institute for Healthcare Improvement.27

These study results are important because nonintensivists such as hospitalists and emergency department physicians can use this technique to provide rapid fluid resuscitation early in the course of severe sepsis and septic shock, when aggressive fluid resuscitation is most effective. Ultrasound imaging of the internal jugular vein is easy to perform without formal training, and the equipment is readily available in most hospitals. Future studies will evaluate outcomes in spontaneously breathing and ventilated patients to determine the accuracy of this measurement technique in volume‐depleted and volume‐overloaded states. If validated in different patient populations, ultrasound measurement of the internal jugular vein could substitute for the EGDT CVP target in critically ill patients and allow early aggressive fluid resuscitation before a central venous catheter is placed.