Key words: hand-carried ultrasound; mechanical ventilation; pulse pressure variation

Transcription

1 Original Research CRITICAL CARE MEDICINE Radial Artery Pulse Pressure Variation Correlates With Brachial Artery Peak Velocity Variation in Ventilated Subjects When Measured by Internal Medicine Residents Using Hand-Carried Ultrasound Devices* J. Matthew Brennan, MD; John E. A. Blair, MD; Chetan Hampole, MD; Sascha Goonewardena, MD; Samip Vasaiwala, MD; Dipak Shah, MD; Kirk T. Spencer, MD; and Gregory A. Schmidt, MD, FCCP Background: Rapid prediction of the effect of volume expansion is crucial in unstable patients receiving mechanical ventilation. Both radial artery pulse pressure variation ( PP) and change of aortic blood flow peak velocity are accurate predictors but may be impractical point-of-care tools. Purpose: We sought to determine whether respiratory changes in the brachial artery blood flow velocity ( Vpeak-BA) as measured by internal medicine residents using a hand-carried ultrasound (HCU) device could provide an accurate corollary to PP in patients receiving mechanical ventilation. Methods: Thirty patients passively receiving volume-control ventilation with preexisting radial artery catheters were enrolled. The brachial artery Doppler signal was recorded and analyzed by blinded internal medicine residents using a HCU device. Simultaneous radial artery pulse wave and central venous pressure recordings (when available) were analyzed by a blinded critical care physician. Results: A Doppler signal was obtained in all 30 subjects. The Vpeak-BA correlated well with PP (r 0.84) with excellent agreement (weighted, 0.82) and limited intraobserver variability ( %) [mean SD]. A Vpeak-BA cutoff of 16% was highly predictive of PP > 13% (sensitivity, 91%; specificity, 95%). A poor correlation existed between the CVP and both Vpeak-BA (r 0.21) and PP (r 0.16). Conclusions: The HCU Doppler assessment of the Vpeak-BA as performed by internal medicine residents is a rapid, noninvasive bedside correlate to PP, and a Vpeak-BA cutoff of 16% may prove useful as a point-of-care tool for the prediction of volume responsiveness in patients receiving mechanical ventilation. (CHEST 2007; 131: ) Key words: hand-carried ultrasound; mechanical ventilation; pulse pressure variation Abbreviations: CVP central venous pressure; HCU hand-carried ultrasound; NPV negative predictive value; PCWP pulmonary capillary wedge pressure; PEEP positive end-expiratory pressure; PPmax pulse pressure maximum; PPmin pulse pressure minimum; PPV positive predictive value; PP radial artery pulse pressure variation; RAP right atrial pressure; RHC right-heart catheterization; VE volume expansion; Vpeak peak blood flow velocity; Vpeak-Ao aortic blood flow peak velocity variation; Vpeak-BA brachial artery blood flow velocity variation; Vt tidal volume Predicting hemodynamic responsiveness to volume expansion (VE) is among the most challenging and important assessments in the acute care setting. In studies 1 12 designed to measure changes in cardiac index following fluid administration in hypotensive patients receiving mechanical ventilation, 28 to 60% of patients showed no significant change. Fluids may not only be ineffective but harmful as well, as suggested by the results of the ARDS Network Fluid and Catheter Treatment Trial. 13 Ideally, one could predict in advance whether fluids will augment perfusion so that the treatment CHEST / 131 / 5/ MAY,

2 focus could shift more rapidly to vasoactive therapy in those who will not respond to fluids. How best to judge fluid responsiveness in the clinical setting is evolving. Physical examination has been shown to be grossly inadequate in the assessment of volume status, For editorial comment see page 1279 and limitations specific to the critical care setting increase the level of error. Traditional markers such as interstitial and pulmonary edema are of limited utility in many disease processes, including sepsis. Limitations to proper patient positioning and the presence of devices designed to secure endotracheal tubes prevent the accurate assessment of the jugular venous pressure. 19,20 While potentially helpful in other clinical scenarios, both right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP) have been shown to be poorly predictive of volume responsiveness. Recently, the safety and utility of right-heart catheterization (RHC) have been questioned, 13,21 24 limiting its availability in some ICU settings. Over the past 5 years, several new tools have emerged to increase the accuracy of the hemodynamic assessment. 4,8,9,11,25 These methods rely on the physiologic interplay between respiration and circulation seen during passive ventilation. Mechanical lung inflation raises pleural pressure, transiently impeding venous return and diminishing right-heart and, subsequently, left-heart stroke volume with each inspiratory cycle. The respirophasic changes in stroke volume reveal themselves in changes in the arterial pulse pressure and the aortic peak flow velocity. What makes this particular cardiopulmonary interaction interesting is its dependence on the dynamics of the patient s individual cardiac output curve. The magnitude of the cyclic variation in stroke volume depends mostly on whether the patient is operating on the steep or the flat portion of the Frank-Starling curve; that is, whether the heart is preload responsive or not. 26 *From the Department of Cardiology (Drs. Brennan, Blair, Hampole, Goonewardena, Vasaiwala, Shah, and Spencer), The University of Chicago Hospitals, Chicago, IL; and the Carver College of Medicine (Dr. Schmidt), University of Iowa, Iowa City, IA. The authors have no conflicts of interest to disclose. Manuscript received July 15, 2006; revision accepted December 14, Reproduction of this article is prohibited without written permission from the American College of Chest Physicians ( org/misc/reprints.shtml). Correspondence to: J. Matthew Brennan, MD, Division of Cardiovascular Diseases, Duke University Medical Center, Erwin Rd, Durham, NC 27710; j.matthew. brennan.98@alum.dartmouth.org DOI: /chest Respirophasic radial artery pulse pressure variation ( PP) has been shown to predict volume responsiveness in hemodynamically unstable patients receiving mechanical ventilation with a positive predictive value (PPV) and a negative predictive value (NPV) of 94% and 96%, respectively. 11 PP is clearly superior to RAP and PCWP as a predictor of volume responsiveness in patients receiving passive mechanical ventilation. However, like the RAP and PCWP, measurement of the PP requires invasive monitoring with a peripheral arterial catheter, which has been associated with a risk of both infectious and embolic complications. 27 In addition, measurement of the PP requires a specialized monitoring setup that is unavailable in many point-of-care settings where initial patient stabilization occurs. Ultrasound technology has been used to address the specific limitations of indwelling arterial and venous catheters. Measurement of the respirophasic aortic blood flow peak velocity variation ( Vpeak- Ao) has been shown to be highly predictive of the response of cardiac output to VE in patients receiving mechanical ventilation, with PPV of 91% and NPV of 100%. 25 The technical expertise and expense involved in obtaining this measurement, however, make it impractical in most ICU settings. Over the past several years, the utility of handcarried ultrasound (HCU) technology in the ICU setting has undergone rapid expansion The sharp learning curve involved with the operation of these machines as well as their portability and affordability have led to the increasing availability of this technology in many acute care settings. The HCU assessment of volume status in spontaneously breathing subjects using the inferior vena cava collapsibility index has been validated. 31 However, the absolute inferior vena cava dimensions have limited utility in the prediction of RAPs in patients receiving mechanical ventilation. 32 Newer-generation HCUs have incorporated Doppler technology and vascular probes as standard features, making the noninvasive bedside measurement of respirophasic variation of peak blood flow velocity ( Vpeak) in peripheral arteries possible. In this study, we sought to determine whether a peripherally measured Vpeak could substitute as an accurate, noninvasive point-of-care surrogate for PP in patients receiving mechanical ventilation. Materials and Methods The research protocol was approved by the institutional review board for human subjects at the University of Chicago Hospitals. Written informed proxy consent was obtained from each subject s next of kin Original Research

3 Patients We studied 30 patients receiving passive mechanical ventilation with clinically indicated peripheral arterial catheters. The patients were enrolled without regard to their body habitus or clinical situation. Exclusion criteria included the absence of sinus rhythm, presence of a ventricular assist device, a contraindication to the prespecified ventilatory parameters (a period of passive ventilation at tidal volume [Vt] 8 ml/kg of predicted body weight and positive end-expiratory pressure [PEEP] of 5 to 10 mm Hg). A medical student performed an initial patient screening and collected subject demographics and clinical history for each patient prior to the collection of peak velocity and pulse pressure data. Brachial Peak Velocity Measurement A SonoSite Titan HCU (SonoSite; Bothell, WA) device with a 5-MHz broadband linear array transducer weighing 7.7 lb at a cost of approximately $40,000 was used to obtain each of the measurements. Two internal medicine residents with minimal exposure to ultrasound techniques were given approximately 30 min of formal instruction in the operation of the HCU and the proper technique for obtaining Doppler measurements from the brachial artery. Ten supervised patient examinations were performed prior to the beginning of the study. Arterial blood flow velocities were measured from the brachial artery just proximal to the antecubital fossa in the arm contralateral to the arterial catheter over 30 s (Fig 1). Residents obtaining ultrasound images were blinded to the results of the arterial pulse pressure variations that were collected independently by a medical student. All image angles were corrected up to 15 for the best signal and stored for immediate review following each measurement. The total period of data acquisition lasted from 2 to 5 min per patient, during which time a 30-s loop of images was obtained. Each 30-s loop was divided into two equal segments for purposes of on-line data analysis. The maximum and minimum peak velocity was recorded from each of the 15-s segments by the medical residents. Velocity variation was calculated for each segment, and the results were averaged to arrive at the mean peak velocity variation for the study interval. Mean intraobserver brachial artery blood flow velocity variation (Vpeak-BA) measurements calculated across the 30 study subjects was % [mean SD]. Vpeak-BA was calculated using the standard formula 25 : Vpeak-BA (%) 100 (peak velocity maximum peak velocity minimum)/[(peak velocity maximum peak velocity minimum)/2]. Vpeak-Ao Arterial pressure and telemetry tracings were recorded over a 30-s interval simultaneously with the ultrasound measurement of the Vpeak-BA collected by a medical student, and analyzed by a boarded critical care physician blinded to the ultrasound results. Systolic and diastolic pressures were measured on a beat-to-beat basis, and pulse pressure was calculated as systolic diastolic pressure. The maximum pulse pressure (PPmax) and minimum pulse pressure (PPmin) values were determined across the 30-s cycle, and the PP was calculated using the following standard formula 11 : PP (%) 100 (PPmax PPmin)/[(PPmax PPmin)/2]. Central Venous Pressure Measurement In the 17 subjects in whom central venous catheters were present, the central venous pressure (CVP) was measured at end-expiration in the standard fashion by a medical student immediately prior to the study interval. Study Protocol Each of the 30 patients was sedated and received mechanical ventilation using volume-control settings with a mean Vt of 9 2 ml/kg and PEEP of 7 2cmH 2 O. All patients received passive mechanical ventilation as judged by ventilator and CVP waveforms (when available), as well as clinical observations made to exclude the recruitment of abdominal muscles. Patients who could not be made passive on the ventilator were excluded from the study, and none received paralytic medications during the trial period. Statistical Analysis Pearson correlation coefficients were calculated as a means of comparing PP with Vpeak-BA and CVP measurements. Using the established PP cutoff of 13%, patients were designated as either predicted responders ( PP 13%) or nonresponders ( PP 13%). Based on this grouping, a receiver operating characteristic curve was developed to establish the most accurate Vpeak-BA cutoff. Based on this cutoff, test performance parameters were determined, including sensitivity, specificity, PPV, NPV, prevalence, and positive and negative likelihood ratios. A Bland-Altman plot 33 was constructed to assess the level of agreement between PP and Vpeak-BA. Weighted values were calculated using contingency tables with PP groupings of 5% (0 to 5%, 5 to 10%, 10 to 15%, 15 to 20%, 20 to 25%, and 25%) as the gold standard. Results The 30 patients included in our study were evenly split between male and female genders, with mean Figure 1. Correlating simultaneous brachial artery image (left, A), brachial artery Doppler recording (top right, B), and pulse pressure recording (bottom right, C). CHEST / 131 / 5/ MAY,

4 age and body mass index of years and 29 8 k/m 2, respectively (Table 1). Twenty of the 30 subjects received IV vasoactive medications, and all but one of the subjects were considered hemodynamically stable (with no change in vasoactive medications, or heart rate or BP changes 10% in the 15-min period before starting the protocol) at the time of investigation. The average mean arterial pressure and heart rate were mm Hg and beats/min, respectively (Table 2). The average respirophasic Vpeak-BA and PP were 13 8% and 11 7%, respectively. A tight, linear positive correlation (r 0.84, Fig 2) was observed between the Vpeak-BA and PP. Using a PP cutoff of 13% to predict response to a fluid challenge (Fig 3), an optimal Vpeak-BA cutoff of 16% was established (area under the receiver operator characteristic curve, 0.947). Test parameters were calculated (Table 3), including sensitivity and specificity of 91% and 95%, respectively. The Bland-Altman plot of variance showed excellent agreement between the two parameters (mean difference, %; Fig 4) and contingency tables constructed to further analyze the level of agreement between Vpeak-BA and PP validated this finding (weighted, 0.82). CVP measurements were available in 17 of the 30 patients (57%), with an average measurement of 10 6 mm Hg. A poor, negative correlation existed between CVP and both Vpeak-BA (r 0.21) and PP (r 0.16). Discussion Traditional static measures of right- or left-sided cardiac pressures are poorly predictive of changes in Table 2 Baseline Hemodynamic Parameters Parameters Mean SD Heart rate, beats/min Mean arterial pressure, mm Hg Respiratory rate, breaths/min 21 6 Vt Vt/ideal body weight, ml/kg 9 2 PEEP, mm Hg 7 2 CVP, mm Hg 10 6 PP, % 11 7 Vpeak-BA, % 13 8 cardiac output that occur with VE in patients receiving passive mechanical ventilation. 3,7,11,34,35 Studies 4,8,11,12 have demonstrated excellent accuracy for the prediction of fluid responsiveness when using dynamic parameters such as PP and Vpeak-Ao. However, the acquisition of these parameters has limitations that may be addressed by measuring Vpeak-BA with an HCU device. Traditionally, static measures of preload obtained through a central venous catheter or RHC have been used as guides to fluid resuscitation in hypotensive patients. However, a large number of studies 11,13,21 24 in patients with trauma, burns, sepsis, or following cardiac surgery, and even in normal volunteers, show that CVP and pulmonary artery occlusion pressure are no better than a coin toss in predicting fluid responsiveness in patients receiving passive ventilation. Keeping with these observations, CVP correlated poorly with PP (r 0.16) in our study. This finding reaffirms the disconnect between static and dynamic parameters and re-emphasizes the importance of using dynamic parameters (eg, PP or Vpeak) to assess fluid responsiveness. Respirophasic pulse pressure and aortic root velocity variations have been shown to be highly accu- Table 1 Subject Demographics* Characteristics Data Age, yr Height, cm Weight, kg Body mass index, kg/m Gender Female 15 (50) Male 15 (50) Race White 16 (53) African American 14 (47) Hypertension 23 (77) Congestive heart failure 8 (27) Diabetes 7 (23) End-stage renal disease 4 (13) Sepsis 5 (17) *Data are presented as mean SD or No. (%). Figure 2. Comparison of pulse pressure variation with bracheal artery peak blood velocity variation Original Research

5 Figure 3. Predicting fluid responsiveness. Predicted favorable response to an IV challenge ( responders ) is based on the PP cutoff of 13%. Patients with PP 13% were predicted most accurately using a cutoff for Vpeak-BA 16%, as shown above. rate indicators of fluid responsiveness in patients receiving passive mechanical ventilation. 11,12 Unfortunately, the acquisition of both PP and Vpeak-Ao has serious limitations. PP relies on an indwelling peripheral arterial catheter, which has been associated with infectious and embolic risk. 27 In addition, the measurement of PP requires a calibrated pressure transducer that is often unavailable in point-ofcare settings, including many military trauma units, emergency departments, and initial ICU evaluations. Likewise, aortic velocity variation requires esophageal intubation with an echocardiographic transducer, an invasive and time-consuming intervention. Indwelling probes that measure variations in aortic blood flow have addressed many of the limitations of this technique and allow for continuous monitoring 36 ; however, the utility of these probes is limited by the need for specialized equipment and software to analyze both aortic diameter and blood velocity. In addition, the variation intrinsic to the measurement of both aortic diameter and blood velocity are compounded by this method and may lead to an unnecessary level of error when predicting volume responsiveness. The use of HCU devices to measure Vpeak-BA provides a practical solution to the limitations of both PP and Vpeak-Ao. Our results demonstrate an excellent correlation and a high level of agreement between the invasively measured PP and noninvasively measured Vpeak-BA using an HCU device. As we have shown, the learning curve for this technique is sufficiently steep to allow its application Table 3 Test Performance Using Vpeak-BA > 16% for the Prediction of Patients With PP > 13% Test Parameters Data Sensitivity 91% Specificity 95% PPV 91% NPV 95% Prevalence 37% Positive likelihood ratio 15 Negative likelihood ratio 0.1 Figure 4. Bland-Altman plot. CHEST / 131 / 5/ MAY,

6 by clinicians with only minimal exposure and training in the field. The technique takes advantage of the rapidly expanding field of HCU technology, and offers a new utility for an increasingly useful tool in the field of acute care medicine. The tight correlation that we have shown between the HCU Vpeak-BA and PP suggests that the ultrasonographic technique may represent an accurate substitute for the more invasive parameter. A Vpeak-BA 16% is highly predictive of a PP 13%, the well-established cutoff for predicting fluid responsiveness in hypotensive patients receiving passive mechanical ventilation. However, the Bland-Altman analysis has shown that clinically meaningful variation does exist between the two techniques, necessitating the validation of the cutoffs for this technique in a study designed to follow changes in cardiac output with VE. Soubrier et al 37 reported the successful use of PP as a predictor of volume responsiveness in spontaneously breathing ICU patients (area under the receiver operating characteristic curve, 0.81). Although the study was limited by a relatively small patient population (n 32) and reported sensitivity and specificity based on a PP of 12% (rather than the established 13% cutoff), the results are promising. The major limitation for the application of this technique to spontaneously breathing patients involves the difficulty of standardizing pleural pressure changes given the potential variation in breath size from patient to patient. Based on the reported results, however, further testing of our method in the spontaneously breathing patient population would be warranted. Limitations This study did not evaluate the utility of Vpeak-BA as a direct predictor of volume responsiveness, as judged by serial cardiac output evaluations using RHC or serial transthoracic echocardiograms. Serial transthoracic echocardiographic evaluations have accuracy limitations, and publications regarding the utility of indwelling RHC have severely limited its use in our patient population, reducing the pool of eligible patients with RHC for enrollment in studies like this. Instead, we chose to compare our technique with PP. Given the excellent performance of this parameter for the prediction of volume responsiveness (PPV, 94%; NPV, 96%), a PP 13% was set as the gold standard for predicting which patients could be expected to respond to an IV fluid challenge with an increase in cardiac output 15%. Several points must also be made regarding the application of any technique that takes advantage of the respirophasic variations in pulse pressure or blood flow velocity to predict volume responsiveness (eg, PP, Vpeak-Ao, Vpeak-BA). First, these methods are not applicable when there are significant arrhythmias. Since varying respiratory rate intervals affect stroke volume, the impact of the ventilator cannot easily be distinguished from that of the arrhythmia. In addition, the accuracy of these techniques in patients receiving mechanical ventilation has been shown to be dependant on an exaggerated change in pleural pressures resulting from Vts 8 ml/kg of predicted body weight and PEEP settings from5to10mmhg. 38 Since many patients receiving mechanical ventilation have acute lung injury and should be receive a Vt of 6 ml/kg of predicted body weight, using any of these methods requires a brief ventilator manipulation to temporarily raise the Vt. It is important also to ensure that patients receiving mechanical ventilation receive passive ventilation for the period of evaluation, since a standardized inspiratory increment in pleural pressure underlies the physiologic basis for the method. Any active ventilatory effort will alter the resulting pleural pressure change and may affect the accuracy of the test. In the modern era of sedative interruption, lung-protective ventilation, and avoidance of paralytic drugs, most patients are active no matter the ventilatory mode. Until further testing is available to judge the accuracy of this method in the spontaneously breathing patient, care must be taken to ensure that the patient is passive by paying careful attention to the patient, the ventilator waveform display, and any intrathoracic vascular catheter tracings. Conclusions Our results have shown that Vpeak-BA is an accurate point-of-care correlate to PP in patients receiving mechanical ventilation, while CVP is not. In our patient population, Vpeak-BA 16% was highly predictive of a PP 13%, the well-established cutoff for predicting volume responsiveness in patients receiving passive ventilation. In addition, this parameter can be measured by clinicians with limited ultrasound expertise using HCU technology after only a brief period of formal training. The use of this technique as a point-of-care tool for the prediction of fluid responsiveness in those critically ill patients in whom PP is either contraindicated or impractical will allow for the more judicious use of IV fluid boluses and potentially a more timely move toward inotropic and vasopressor medications in critically ill patients receiving passive ventilation. Future studies are needed to validate our Vpeak-BA cutoff in patients receiving passive ven Original Research

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