Like musical notes, physiologic waveforms (e.g., BP) can be described as the sum of a series of sine waves, each with its own amplitude, frequency, and phase shift. The dominant waveforms, whose frequencies center around multiples of the fundamental frequency, are known as “harmonics.”3 The VERIFI algorithm decomposes the volume signal, V(t), into frequency components using frequency domain analysis (e.g., Fourier transformation). Pulsatile volume, VAC(t), low frequency volume, VLF(t), and very low frequency volume, VVLF(t), are isolated. Because volume changes are a function of pressure changes, volume and pressure can be related to each other by the degree of amplification, also known as “gain” (G, analogous to the resistance in Ohm’s law). Gain is assumed to be zero at very low frequencies, but at the “pulsatile” and low frequencies (GAC, GLV, respectively) can be determined by comparing various fixed cuff pressures to the signal amplitude and developing a transfer function (T) relating the 2 (Fig. 5).67 For a comparison of the features of the Nexfin/ClearSight and CNAP devices, see Table 2.68
As with sphygmomanometry and oscillometry, volume clamp devices require peripheral perfusion and blood flow to estimate BP. In theory, just as the pulse oximetry waveform (which is derived from both red and infrared PPG signals) is affected by extreme vasoconstriction, temperature changes, and other physiologic disturbances, the same should be true of volume clamp estimates of BP.
The impact of vasomotor tone on this class of devices has been studied. An early analysis of the Finapres device during surgery found that half of the measurements were conducted in a state of vasoconstriction (defined as a PPG amplitude reduction of at least 50% [PPG amplitude is generally considered an acceptable surrogate measure for vasomotor tone69]). This small study, in which 378 paired measurements were made in 6 subjects, suggested that the discrepancy between volume clamp and oscillometric devices was dependent on peripheral perfusion.70 Interestingly, a direct comparison between the Finapres and the invasive measurements suggests that the thumb is the optimal site for finger arterial BP measurements, presumably because of the larger arterial cross-sectional area and better perfusion.71
In a meta-analysis of studies comparing commercially available noninvasive arterial BP measurements with invasive measurements, the overall random-effects pooled SD was 9.4 mm Hg for MAP using the CNAP, slightly worse than the 8.4 mm Hg reported for all noninvasive devices overall.41 This study did not specifically analyze data for the Nexfin or ClearSight devices. Because a true gold standard is readily available (direct arterial catheterization), volume clamp devices will always be less accurate than the gold standard. The important clinical question is how well the volume clamp devices agree with direct catheterization, and how this compares with other noninvasive devices (e.g., oscillometry). However, as examined in an aforementioned study comparing oscillometry and direct arterial catheterizations, as the true BP deviated from the mode, oscillometric performance deteriorated, particularly at the extremes (hypertension, hypotension) when accurate measurements matter the most.40
There have been multiple comparisons of volume clamp devices with direct arterial catheterization. Because this body of work spans several decades, not all of them use the same statistical techniques. More modern studies use the limits-of-agreement approach. Overall, these data suggest performance that is at least comparable to oscillometric techniques, although there are no large, retrospective comparisons available to validate the prospective observations in the real-world clinical environment (Table 3).72–96
In addition to giving the clinician a near-instantaneous measurement of systolic, diastolic, and MAPs, arterial catheterization also allows for convenient, periodic blood sampling (e.g., for the measurement of arterial blood gases). Analysis of >12,000 surgical cases at an Academic Medical Center in the United States revealed that 16% of patients were monitored with an arterial catheter.97 By 1990, >8 million had been placed.98
A variety of algorithms designed to measure stroke volume (SV) and fluid responsiveness (e.g., pulse pressure variation, SV variation) based on sophisticated analysis of the arterial waveform have been developed.99 Until the appearance of the volume clamp technique devices on the market, noninvasive estimates of SV, pulse pressure variation, and SV variation required placement of an intraarterial catheter. Now, with the availability of the ClearSight and the CNAP, the same algorithms can be applied to an arterial pressure waveform derived from the volume clamp technique. At present, there are insufficient clinical data to comment on the relative accuracy of noninvasive SV derived from directly or indirectly measured arterial pressure waveforms.
That said, volume clamp devices, which seem to outperform automated oscillometric techniques in terms of accuracy and measurement frequency, may one day change the anesthesiologist’s decision-making process with regard to BP monitoring.100 This is particularly important, as the complications associated with percutaneous cannulation of a systemic artery, including infection, pseudoaneurysm formation, nerve injury, permanent arterial occlusion, or hematoma formation, are increasingly appreciated.101–103
Arterial BP is most commonly measured at the radial, brachial (or axillary), and femoral sites, with the radial being most common.103 As described earlier, the BP waveform is a function of both incident and reflected waves and is dependent on arterial compliance, branch points, and distance from the left ventricle. Thus, different arteries produce different BP tracings within the same individual.
Arterial cannulation can be performed using a variety of techniques. The simplest strategy is to insert a 20-gauge (or smaller) catheter directly into the artery and “thread” the catheter off a needle and into the artery. Some clinicians prefer to “transfix” the artery with a needle and catheter, remove the needle, and retract the catheter backward until it resides in the vessel lumen, after which a guidewire can be inserted through the catheter and into the artery. For particularly challenging patients, the Seldinger technique can be used, in which a needle is inserted into the vessel, a guidewire is threaded through the needle and into the vessel, the needle is removed, and the catheter is threaded into the vessel (over the wire). Identification of the artery may be facilitated by using ultrasound guidance.104 A meta-analysis of 7 trials including 482 patients suggested that ultrasound-guided radial artery cannulation increased the first-attempt success rate, as well as decreasing the number of attempts, time to success, and rate of hematoma formation.105
Some clinicians use the “Allen test” to evaluate collateral flow to the hand before cannulating the radial artery. This test is performed by occluding arterial inflow into the hand (by compressing both the radial and the ulnar arteries simultaneously) while asking the patient to create a fist, thereby exsanguinating the palm. After opening the hand and releasing the pressure over the ulnar artery (but maintaining pressure over the radial artery), a qualitative sense of the adequacy of ulnar flow can be gained by observing how quickly the palm returns to color. Although the Allen test seems logical, it is not clear that reason and reality have aligned, because large analyses including several thousand patients have questioned the predictive ability of the Allen test.106,107 Furthermore, it is now appreciated that the radial artery can often be harvested for coronary bypass surgery, despite an abnormal Allen test, and this has prompted some investigators to look for alternative testing modalities.108,109
Intraarterial pressure is measured using a strain gauge, the essential component of which is a thin metal wire whose resistive properties change as it is stressed. By building strain gauges into a Wheatstone bridge circuit, changes in strain can be measured as electrical current through the bridge fluctuates. These changes in current can be translated into pressure changes by “zeroing” the transducer. Importantly, current intraarterial pressure monitors measure the pressure of a fluid-filled column that is in hydrostatic continuity with the blood stream. Thus, the physical attributes of the measuring system—in particular, the length, diameter, and stiffness of tubing—can potentially affect the measured BP waveform.
The fluid-filled transduction systems that are commonly used to transmit intravascular pressure changes to a Wheatstone bridge strain gauge can be described as “underdampened, second-order dynamic systems.”110 Three parameters define the performance characteristics of these systems: mass (of fluid), elasticity (of tubing), and friction (primarily between the fluid and the tubing). Every fluid-filled tubing system has a natural frequency (fn), that is, a frequency at which a pressure pulse will oscillate within the system, and a damping coefficient (ζ), a measure of how quickly an oscillating waveform will decay. Fluid-filled transduction systems are “underdampened” because a pressure pulse will oscillate at the natural frequency of the system before decay. Rigid, short, narrow diameter tubing more rapidly transmits pressure waveforms, effectively increasing the natural frequency. Dampening is a function of energy loss, which occurs primarily because of friction. Air bubbles, tubing kinks, stopcocks, and other irregularities can alter the physical characteristics of the tubing system and distort the recorded waveform.
Depending on the complexity of the BP waveform, as many as 10 harmonics may be required to accurately reproduce the BP.3,110 Because the human heart rate is approximately 1 to 2 Hz (60–120 beats/min), higher-order harmonics may approach 20 Hz in frequency. To faithfully reproduce these higher-order harmonics, a natural frequency as high as 40 Hz is needed. The natural frequency of systems used clinically can be considerably lower than this.111
Measurement of intraarterial BP is relatively straightforward if the aforementioned principles on which the measurement system is based are understood. One common mistake is to attribute high systolic BPs to “whip” or an under-responsive system. Although it is possible for an under-responsive system to augment pulse pressure (thus raising systolic pressure and lowering diastolic pressure), this theory can be tested by performing a flush test, measuring both assess fn and ζ and plotting the performance characteristics of the transduction system on a dynamic response map. In reality, it is normal for pulse pressure to increase as the measurement site moves distally, particularly in patients with noncompliant vasculature. This widened pulse pressure should initially be assumed to be real and only attributed to suboptimal equipment after a determination of both fn and ζ has been made.
The BP waveform can be mathematically decomposed into a series of sine waves, each described by their amplitude, frequency, and phase shift. This is accomplished using a computational technique called “fast Fourier transformation.” The fundamental frequency of the BP waveform is the heart rate (for a heart rate of 80 beats per minute, the fundamental frequency is 1.33 Hz or 1.33 beats per second). When “harmonic” waves are added to the fundamental wave, the true shape of the waveform is more accurately approximated.
Although pseudoaneurysm formation, nerve injury, permanent arterial occlusion, and hematoma formation are known complications of intraarterial catheterization, the risk of infection is increasingly appreciated.101–103 An analysis of over 200 published studies on infectious complications associated with intravascular devices estimates an infection rate of 1.7 per 1000 catheter-days for arterial catheters, when compared with 0.5 per 1000 for peripheral IV catheters and 2.7 per 1000 for nontunneled central venous catheters.102 A large, factorial trial analyzing the impact of dressing changes and chlorhexidine-impregnated sponge use on both central venous and arterial catheters demonstrated a substantially lower rate of bloodstream infections (hazard ratio, 0.39; 95% CI, 0.17–0.93), suggesting that these devices should be placed on all arterial catheters.112
Assuming that anesthesiologists desire to maintain BP within some prespecified range, a feedback loop must be established among the patient, the BP monitor, and the anesthesiologist. Feedback loops are well described in the engineering literature.113 A rudimentary feedback loop consists of a measurable variable (e.g., temperature), a method of measurement (e.g., thermometer), and a response (e.g., heating or cooling). The “set point” is the ideal value for the measured variable (e.g., 37°C). In the simplest feedback loop, the response is linearly related to the difference between the measured process variable and the set point. The magnitude of the response, indexed to this difference (known as an error value), is known as gain. This type of system is often referred to as a proportional–integral–derivative controller.
In real life, there is often a time delay associated with the detection of an abnormality both in the measured variable and in the response (known as response time). In a fairly stable system with minimal response time, large amounts of gain can exert substantial control over the measured variable. However, if the response time is long (either because there is measurement delay or it takes time to affect the measured variable [e.g., application of heat to a cold patient]), it is possible for the system to be overgained, a situation in which an overly aggressive response destabilizes the system. Conversely, an undergained system may never exert control of the measured variable because the response is not effective enough. Ultimately, the stability of a simplified feedback loop system is a function of the inherent variability in the measured variable, response time, and gain.
Although, on the surface, this may seem to have only academic value, a thorough understanding of feedback loops is of great relevance to the anesthesiologist. For instance, an anesthesiologist who only administers 5-μg doses of phenylephrine may never be able to exert meaningful control over BP (nor will the anesthesiologist who administers 500 μg at a time). Similarly, BP stability is more easily achieved when near-instantaneous measures are used, as opposed to an oscillometric cuff that makes periodic measurements every 5 minutes. Also important is an appreciation for the lag time associated with these interventions; phenylephrine, for instance, takes 42 seconds to achieve peak effect.114 Appreciation for these basic engineering principles among anesthesiologists is not widespread, and they are not part of the American Board of Anesthesiology content outline. Nonetheless, basic instruction on the principles of feedback loops may be a high-yield endeavor for anesthesiology trainees.
Investigators at the University of California, Irvine, have taken the concept of feedback loops one step further and are attempting to “close the loop” using algorithms, which mimic the decision-making process used by individual anesthesiologists. The basic argument for this approach is that if some aspects of hemodynamic management can be easily standardized (e.g., giving IV fluid based on preestablished triggers), an automated feedback system that constantly monitors the measured variable (in this case, BP) will outperform a human being by minimizing response time, in addition to freeing up the anesthesiologist to focus on more cognitively challenging tasks. Preliminary work by this group has demonstrated feasibility and safety, but prospective comparisons between traditional, human-directed hemodynamic management and closed-loop hemodynamic management have yet to be undertaken.115,116
Periodic, quantitative measurement of BP in humans, predating the era of evidence-based medicine by over a century, is a component of the American Society of Anesthesiologists standards for basic anesthetic monitoring and is a staple of anesthetic management worldwide. Thus, it is unlikely that the clinical value of BP monitoring will ever be assessed in prospective fashion. Furthermore, adherence to traditional BP parameters complicates the ability of investigators to determine whether particular BP ranges confer any clinical benefits. The BP waveform is a complex amalgamation of both antegrade and retrograde (reflected) pressure waves and is affected by vascular compliance, distance from the left ventricle, and the 3D structure of the vascular tree. Accurate reproduction of this waveform requires an appropriately engineered monitoring system with a frequency response of up to 40 Hz. Oscillometry is the standard method of measuring BP semicontinuously in anesthetized patients and is the primary form of measurement in >80% of general anesthetics. Although these devices perform reasonably well when true MAP is approximately 75 mm Hg, a major shortcoming of oscillometry is its poor performance at the extremes. Another shortcoming of these devices is that they offer no information about the shape of the BP waveform. Two classes of devices have been developed to measure the BP waveform continuously, without requiring the placement of a catheter. Tonometric devices “touch” the radial artery by applying external pressure to the wrist. Volume clamp devices combine a rapidly responsive finger cuff to a finger plethysmograph in an effort to keep the radial artery in an “unstretched” state and the PPG flat; the finger cuff pressure required to do so closely approximates the radial artery pressure. The limits-of-agreement analyses of the latter 2 device classes using invasive measures as a reference standard are promising. Arterial catheterization remains the gold standard for accurate BP measurement, and understanding the measurement system is necessary for proper interpretation of the waveforms. In particular, the frequency response and damping coefficient of the fluid-filled tubing system can be used to measure the dynamic response of the system, and thus its adequacy for the accurate reproduction of complex waveforms. Fortunately, both the frequency response and the damping coefficient can be measured at the bedside using the flush test. Control of BP requires measurement, an algorithm (usually human-controlled) and an intervention. This can be described as a feedback loop, of which gain and response times are important variables that affect the stability of the measured variable (in this case, BP). Several investigators have begun “closing” this loop, effectively automating the human algorithms used to manage BP, allowing the anesthesia providers to focus their intellectual energy on other, more complex decisions and tasks.
a Available at: http://www.asahq.org/~/media/Sites/ASAHQ/Files/Public/Resources/standards-guidelines/standards-for-basic-anesthetic-monitoring.pdf. Accessed February 1, 2016.
b Available at: http://www.cnsystems.com/Innovation/Cnap-Technology. Accessed February 1, 2016.
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