Continuous noninvasive monitoring of arterial pressure using the vascular unloading technique in comparison to the invasive gold standard in elderly comorbid patients: A prospective observational study

Abstract Background and Aims Elderly patients aged ≥65 years represent a growing population in the perioperative field, particularly orthopedic and vascular surgery. The higher degree of age‐related or comorbid‐dependent vascular alterations renders these patients at risk for hemodynamic complications and likely denote a possible limitation for modern, non‐invasive arterial pressure monitoring devices. The aim was to compare vascular unloading technique‐derived to invasive measurements of systolic (SAP), diastolic (DAP), and mean arterial pressure (MAP) in elderly perioperative patients. Methods This prospective observational study included patients aged ≥65 years scheduled for orthopedic and patients ≥50 years with peripheral artery disease Fontaine stage ≥ II scheduled for vascular surgery, respectively. Invasive radial artery and non‐invasive finger‐cuff (Nexfin system) arterial pressures were recorded before and after induction of general anesthesia and during surgery. Correlation, Bland‐Altman, and concordance analyses were performed. Measurements of arterial pressure were also compared during intraoperative hypotension (MAP <70 mm Hg) and hypertension (MAP >105 mm Hg). Results Sixty patients with orthopedic (N = 25, mean (SD) age 77 (5) years) and vascular surgery (N = 35, age 69 [10] years) were enrolled. Seven hundred data pairs of all patients were analysed and pooled bias and percentage error were: SAP: 14.43 mm Hg, 43.79%; DAP: −2.40 mm Hg, 53.78% and MAP: 1.73 mm Hg, 45.05%. Concordance rates were 84.01% for SAP, 77.87% for DAP, and 86.47% for MAP. Predefined criteria for interchangeability of absolute and trending values could neither be reached in the overall nor in the subgroup analyses orthopedic vs vascular surgery. During hypertension, percentage error was found to be lowest for all pressure values, still not reaching predefined criteria. Conclusion Arterial pressure monitoring with the vascular unloading technique did not reach criteria of interchangeability for absolute and trending values. Nevertheless, the putatively beneficial use of noninvasive arterial pressure measurements should be further evaluated in the elderly perioperative patient.

Predefined criteria for interchangeability of absolute and trending values could neither be reached in the overall nor in the subgroup analyses orthopedic vs vascular surgery. During hypertension, percentage error was found to be lowest for all pressure values, still not reaching predefined criteria.
Conclusion: Arterial pressure monitoring with the vascular unloading technique did not reach criteria of interchangeability for absolute and trending values. Nevertheless, the putatively beneficial use of noninvasive arterial pressure measurements should be further evaluated in the elderly perioperative patient. The proportion of elderly patients aged ≥65 years is steadily increasing in the perioperative, particularly orthopedic, and vascular surgical setting. [1][2][3] These patients generally exhibit a higher level of aging-related cardiovascular alterations including atherosclerosis. 4,5 As this cohort may be particular susceptible to hyoptension during anesthesia, sufficient perioperative hemodynamic monitoring is a central task for patient safety. 6,7 Blood pressure measurement is one key factor and is most commonly performed using the the noninvasive oscillometric method with an inflatable cuff at the upper limb. 8 However, the gold standard is the continuous invasive beat to beat blood pressure monitoring using an arterial line. 9 An attractive alternative are completely noninvasive continuous monitoring devices using the "vascular-unloading technique," introduced by Penaz. 10 This method records the pulse wave of the peripheral arterial blood volume by an optical plethysmograph mounted in an inflatable finger cuff 11 and has the advantage of providing continuous arterial pressure measurements without the inherent risk of invasive monitoring. 12 This noninvasive technique using different devices has already been investigated for its valid application for blood pressure monitoring in different clinical settings and patient categories, compared to either invasive or noninvasive blood pressure measurement. [13][14][15][16][17] Poor performance of noninvasive finger blood pressure monitoring was mostly related to critically ill patients and clinical situations with reduced perfusion due to severe hypotension, disease-related peripheral oedema, use of vasopressors or hypothermia. 18,19 Furthermore, an early study described age-dependent differences in the clinical reliabilty of arterial pressure measurements due to a degenerative decline in peripheral reflection coefficient resulting from decreased distensibility of peripheral arteries. 20 However, information regarding the application of noninvasive monitoring devices specifically in the group of elderly patients in the perioperative setting is limited. The higher degree of age-related or comorbid-dependent vascular alterations in the elderly likely denotes a possible limitation of the vascular-unloading technique. 21,22 Therefore, the aim of the presented study was to test the interchangeability of blood pressure measurements using the vascular unloading technique (Nexfin finger-cuff device) compared to the invasive gold standard of an arterial line in elderly patients scheduled for orthopedic and vascular surgery.

| Intrumentation and study protocol
The standard anesthesia monitoring was established as follows: pulse oximetry, electrocardiography, and noninvasive blood pressure measurement taken by a cuff at the upper limb. The arterial line (Arrow R Intl., Reading, Pennsylvania; Transducer: DPT-6000, CODAN pvb Critical Care GmbH, Forstinning, Germany) was placed under local anesthesia in Seldinger technique in the radial artery on the same side as the finger cuff, in accordance to previous study protocols. 15,23,24 All patients were then connected to the noninvasive Nexfin monitoring system (BMEYE, Amsterdam, The Netherlands) being recently distributed as the Clearsight system (Edwards Lifesciences, Irvine, California). 25 The technique of this finger cuff-based device has been described in detail before. 11 The correct size of the finger cuff belonging to the system was choosen and placed at the middle phalanx of the index finger ipsilateral to the reference arterial line and connected to the wrist unit and heart reference system. This system adjusts the blood pressure to hydrostatic differences between the sensor and the heart level. The Nexfin monitor was connected to the wrist unit and the measurement procedure started in accordance to the user manual.
Obvious artifacts of the invasive and noninvasive-derived arterial pressure measurements were excluded after visual inspection of the arterial pressure waveforms.

| Data collection
The study protocol is illustrated in Figure 1 Hypotension was defined as MAP below 70 mm Hg and hypertension as MAP higher than 105 mm Hg. 26,27 These recordings were treated as a single measurement and analyzed separately. Demographic data including gender, age, height and weight, ASA classification, comorbidities, and type of surgery were collected from all study participants.

| Statistical analysis
The recommended Association for the Advancement of Medical Instrumentation (AAMI) criterion of a mean difference ≤5 mm Hg and associated SD of ≤8 mm Hg 28 between the Nexfin-and invasively derived arterial pressure values was defined as the primary endpoint for the cohort of elderly perioperative patients. With 98% power at an alpha level of α = 5%, the minimum required sample size for the effect size of 5/8 = 0.625 was calculated to be at least 44 (two-sided, one sample t test, G Power software, Düsseldorf, Germany). AAMI recommends a minimum sample size of 85 patients, although comparisons of continuous, finger-cuff arterial pressure measurements with an invasive reference method are excluded by this standard. 28 Thus, we deemed a sample size of 60 participants to be sufficient according to previous study protocols. 29 Normal distribution of the outcomes was checked and verified by visual inspection of the histogram analysis. Pearson correlation analysis of measurement pairs for SAP, DAP, and MAP between the two monitoring devices was performed. Bland-Altman analysis was used for the comparison of the paired arterial pressure measurements with calculation of the mean difference (bias) and limits of agreement (LOA) defined as the SD of the bias times 1.96. 30 Differences were compared with the aforementioned AAMI criterion for interchangeability. 28 The percentage error (PE) was calculated (1.96 SD of bias/[invasive arterial pressure/2] to quantify the F I G U R E 1 Study protocol with corresponding hemodynamic measurement time points. DAP, diastolic arterial pressure; MAP, mean arterial pressure; SAP, systolic arterial pressure relative differences between both measurement techniques as an additional statistical estimate with acceptable cut-off values at 14.7% for SAP, 17.5% for DAP, and 18.7% for MAP as reported by Ilies et al. 15 Finally, an analysis of concordance was conducted in order to evaluate the trending abilitity of the Nexfin system. The concordance was calculated as the percentage of measurement pairs with the same direction of change after exclusion of pairs with a change <5% in order to increase the signal-to-noise ratio. Based on the data points outside the exclusion zone, we calculated the concordance rate as the proportion (percentage) of concordant data pairs to all data pairs with an acceptable ability to show hemodynamic trends when the level of concordance was >92%. 31 A P value of <.05 was considered as statistically significant. Statistical analysis was performed using SPSS Statistics 21 for Windows (IBM; Armonk, New York).

| Arterial pressure values in the orthopedic and vascular surgery groups and during hypotension and hypertension
F I G U R E 5 Bland-Altman analysis of the mean arterial pressure between Nexfin and invasive reference during hypotension and hypertension. Bland-Altman plot of the differences vs the means of paired mean arterial pressure measurements between the invasive and noninvasive method in patients with hypotension (A) and hypertension (B). The lines correspond to the mean difference (bias) and 95% limits of agreement (SD of the bias times 1.96). In addition, the value for the calculated percentage error (PE) is displayed in the diagram  29 The three studies included in this meta-analysis using Interestingly, the best agreement was detected in hypotensive periods as opposed to our findings with the highest PE found for DAP during hypotension. Previous studies also described a rather poor performance of the Nexfin device and pulse contour analysis techniques during hypotension. 18,19,38 In a prospective study by Alfano et al, 13 the vascular unloading technique did not correspond to oscillometric blood pressure recordings in 40 hemodynamically stable patients requiring hemodialysis. The authors suggested that the reason for the poor results of the Nexfin system might be related to the high prevalence of vasculopathy in their patient cohort with a mean age of 68.9 years. 13 In accordance to our study, best results were shown for MAP and SAP while performance for DAP again was worst. The diastole marks the lowest part of the arterial curve between two heartbeats. So it appears likely that the precision of the diastole recordings might be even more impaired by coexisting atherosclerotic alterations in the small peripheral vessels of the fingers, compared to the radial artery of the arm. Gizdulich et al evaluated the performance of the Finapres method which is also based on the vascular unloading technique. In 53 healthy participants, they were able to show that SAP in the finger measured by the Finapres was significantly higher than in the brachial artery while DAP was concomitantly underestimated by the device. 39 The authors interpreted their finding with a pulse wave reflection and pressure gradient due to the blood flow raising toward the vessels of the periphery. The resulting postulated model to convert finger pressure waveforms to brachial pulsation was then taken as the basis for the Nexfin algorithm. 39 In elderly subjects and patients with signs of arteriosclerotic vascular disease, finger arterial pulse pressure is considered to be lower than the pulse pressure measured in the brachial artery, resulting in damped finger pulse pressure. In an early study in 39 patients undergoing diagnostic cardiac catheterization, O'Rourke et al showed that the mentioned pulse wave reflections lead to a rising systolic pressure in the periphery. 20 While a diastolic wave toward the periphery was found particularly in younger participants, waveform reflection could barely be shown in older patients with atherosclerotic lesions, so that no diastolic wave was found. Thus, the accuracy of the noninvasive finger-cuff technology might not only be hampered in patients with pre-existing peripheral artery disease but also in the elderly due to an age-associated arteriosclerosis with consecutive arterial stiffness and decline in vascular function, loss of arterial wall compliance and peripheral perfusion. 4,5 Van Ittersum et al already described differences between sphygmomanometric and oscillometric arterial pressure measurement devices dependent on the presence of diabetes. 40  size. This "gap in validation protocols" is also acknowledged in the recent AAMI/ESH/ISO collaboration statement where the task group consented that separate validation protocols need to be developed for specific functions of certain blood pressure measurement devices including continuous techniques. 42 Another limitation is that the ipsilateral measurement of intra-arterial pressure from the reference radial line likely introduced bias for the finger cuff photopletysmography-based measurements of the small finger arteries. 43 Contralateral measurements could have also introduced bias in our patient cohort due to potential differences in vessel architecture and the degree of atherosclerosis. We did not use doppler ultrasound sonography in order to evaluate peripheral arm perfusion at baseline but decided to use the same arm for both devices in accordance to previous, comparable study protocols. 11,15,44 Moreover, the subanalyses of hypo and hypertension are limited due to the small sample of measurements, in particular for the analysis of hemodynamic pressure trending ability where the detected changes of the blood pressure often were to small (<5%) between two measurements for a valid calculation and subsequent exclusion as per definition. In comparison, our study isto our knowledge-the first systematic investigation of noninvasive and invasive arterial pressure measurements in elderly patients with and without preexisting peripheral artery disease.

| CONCLUSION
In conclusion, noninvasive arterial pressure measurement using the vascular unloading technique (Nexfin finger-cuff technology) in the perioperative phase of elderly or vascular comorbid patients, respectively was not interchangeable with the gold standard of invasive arterial line measurement. Our findings underline further demand of larger clinical trials to better evaluate the useability of noninvasive measurement devices in this growing proportion of perioperative patients.

FUNDING
No external funding was received for this study.

CONFLICT OF INTEREST
All authors have provided information on potential conflicts of interests directly or indirectly related to the work submitted and filled out the ICMJE disclosure forms. All authors declare that they have no conflict of interest. The corresponding author Gunnar Elke confirms that he had full access to all of the data in the study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis.

TRANSPARENCY STATEMENT
The corresponding author Gunnar Elke confirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.