Abstract
Objectives
Reactive hyperaemia following thigh compression increases arterial inflow and venous outflow. The net effect can be measured by changes in calf volume quantified using air-plethysmography. The objective was to investigate the effect of thigh compression on venous return.
Method
The right legs of 19 consecutive volunteers (14 male), median age 31 (25–56) years, were studied in the supine position using air-plethysmography. The clinical, etiological, anatomical, pathophysiological (CEAP) class was C0. A thigh-cuff, 12 cm wide, was inflated in increments of 10 mmHg, from 0 to 80 mmHg. After each inflation step, the calf volume increased to a plateau and was recorded. At 80 mmHg, the thigh-cuff was deflated suddenly with the calf volume decreasing until baseline. Calf volume changes were recorded and stored for analysis.
Results
There was a stepwise increase in the venous volume of the calf with each incremental rise in thigh-cuff pressure up to 80 mmHg (p < .0005, Friedman). The median (interquartile range) increase in venous volume from 0 to 80 mmHg was 87 (65–113) mL (p < .0005, Wilcoxon). The volume change below the original baseline following thigh-cuff release was −16 (−12 to −25) mL (p < .0005, Wilcoxon).
Conclusions
Once optimised, intermittent pneumatic compression of the thigh may have a therapeutic role in augmenting the venous return and reducing leg swelling in patients.
Keywords
Introduction
In health, the volume of the leg is maintained at equilibrium where the amount of arterial blood entering the leg is equal to the amount of venous blood (and lymph) returning to the heart. Temporary situations which affect the arterial supply or the venous outflow will lead to an acute change in leg volume up to the next point of equilibrium until arterial inflow matches venous outflow. These acute changes in volume can be recorded using air-plethysmography (APG) and represent the net effect of inflow and outflow.
Temporary arterial occlusion leads to a profound increase in blood flow when the occlusion is released. This is termed reactive hyperaemia. It can be defined as the rapid, large increase in blood flow that is a reaction to the release of a brief circulatory obstruction. Temporary venous obstruction is not painful unlike arterial occlusion and may result in a similar response. What is not known is whether the net effect of a temporary venous obstruction results in a net increase or decrease in the venous return.
Compression is used extensively in clinical practice to augment the venous return. It can be applied in the form of elastic or inelastic bandages, stockings or by intermittent pneumatic compression pumps. The clinical aim is usually to reduce oedema, prevent/treat deep vein thrombosis and the post-thrombotic syndrome and prevent/heal venous ulcers. However, this compression is directly applied over the calf or the thigh and calf, but never over the thigh in isolation. Differential effects of calf compression alone versus calf and thigh compression have been reported recently using compression stockings and APG. This was a study on 40 legs with post-thrombotic syndrome that failed to observe any differences in the reduction of reflux (venous filling) with stockings of stronger compression strength or above-knee versus below-knee length. 1 Pre-existing information on the isolated effect of thigh compression on calf volume changes rests with earlier studies using APG. However, these did not report the differences between calf volumes before and after a brief period of thigh compression.2,3
The hypothesis of the current study is that intermittent pneumatic compression directly over the thigh causes physiological alterations which on release of the compression may reduce calf volume, thus indicating a net augmentation of venous return (Figure 1). The aim of this study was to measure the net effect of intermittent thigh compression on the volume of the calf.
Leg volume increases and plateaus during thigh-cuff inflations from 0 mmHg (a) to 80 mmHg (b). When the thigh-cuff is suddenly deflated to 0 mmHg again (c), the leg volume decreases to below the original baseline.
Methods
Study design
This was a prospective study on the right leg of 19 consecutive healthy volunteers. The right leg was chosen for convenience because it was the closest to the apparatus. The study took place in a single research laboratory under a standardised environment. Informed consent was obtained from all participants. The protocol provided the pilot data for a larger study on patients which was granted full ethical approval.
Procedure
Participants were requested to lie supine on an examination couch with the head resting on a pillow and the heel of the right leg elevated on a rigid foam support cushion 20 cm high. The leg was externally rotated with the knee flexed slightly to prevent any impediment to venous return at the popliteal fossa.
4
A cuff (Hokanson®), 12 cm wide, was placed around the upper thigh and attached to a pneumatic inflation/deflation pump (VenaPulse®). This provided inflation pressures under the control of the operator with a rapid inflation rise time of <300 ms and a foot pedal for rapid deflation. The same size thigh-cuff was used in all the subjects, irrespective of thigh girth. An air-filled sensor cuff, which is part of the APG apparatus (ACI Medical LLC, San Marcos, CA, USA), was placed around the calf to record changes in volume.
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This was attached to an air-pump pressure/voltage transducer and after 5 min of rest calibrated with 100 mL of air so that changes in voltage could be converted to changes in volume. The traces obtained were displayed on a monitor using sensitive recording software (WinDaq® apparatus from DataQ®) and stored for analysis at study completion. The apparatus is illustrated in Figure 2.
The apparatus used. The air-plethysmograph sensor calf-cuff is first calibrated using an inflation/deflation of 100 mL of air. The calf volume changes are then recorded on software in response to thigh-cuff inflation and deflation manoeuvres.
Initially, the thigh-cuff was inflated to 10 mmHg and the resulting change in calf volume was then observed on the monitor. When a plateau was reached, the thigh-cuff was inflated from 10 mmHg to 20 mmHg for the next plateau. This was repeated in steps of 10 mmHg until the 80 mmHg plateau. The thigh-cuff was then deflated suddenly. The recording was completed when the volume of the calf decreased to a new baseline (Figure 3). A manual flick of the sensor calf-cuff was used to mark the inflation events as a spike on the tracing, with the number of spikes corresponding to each multiple of 10 mmHg rise in inflation pressure (Figure 3).
Increase in calf volume (vertical axis) in response to 10 mmHg increases in thigh-cuff pressure from 10 to 80 mmHg (depicted just to the right of the event spikes). At the 80 mmHg plateau, the thigh-cuff is deflated to illustrate the venous return curve. Horizontal dotted lines represent the difference between the inflow and outflow volumes.
Parameters measured
All the measurements were taken from the subject’s calf volume versus time chart (Figure 3). The software allowed the chart to be expanded horizontally for better visualisation by scaling the time variable. This allowed the screen cursor to pinpoint and display the measurements with greater accuracy. The voltage change caused by the injection and aspiration of 100 mL of air in the calibration syringe allowed the voltage recorded on the vertical axis to be calibrated into volume. The amplitude of the pulsations observed was measured in Volts using the mean of four consecutive pulsations at the 10 mmHg and 80 mmHg thigh-cuff inflations, respectively. This was performed in order to quantify the increase in intensity of the pulsations at the higher thigh-cuff inflation pressures. The following were measured:
Inflow volume (mL). This is the volume change from baseline at 0 mmHg to the 80 mmHg plateau point. Outflow volume (mL). This is the volume change from the 80 mmHg plateau point to the baseline achieved after the thigh-cuff has been deflated. Volume decrease (mL). This is the difference between the inflow and outflow volumes and represents the decrease in calf volume compared to the original baseline. The venous emptying time (VET90 in s). This is the time taken for the calf to empty 90% of its outflow volume. It represents the rate of venous emptying towards the end of the outflow curve. Outflow fraction (%). This is the absolute volume decrease of the calf during 1 s following thigh-cuff deflation expressed as a percentage of either the inflow or the outflow volume. It represents the rate of venous emptying towards the beginning of the outflow curve.
The rate of venous emptying, as described in (iv) and (v) above, was assessed primarily to determine whether a faster rate was associated with a greater amount of additional venous emptying.
Statistical analysis
Data were collected onto spreadsheets for each subject in the study and transferred into the IBM® SPSS® statistics package version 19 (IBM Corporation, Armonk, NY, USA) at completion. Medians, interquartile ranges (IQR) and ranges were used to describe the data using boxplots, with outliers represented as a small circle. Means with standard deviations were also used for ease of reference because this format was common in earlier publications by other authors on APG. The non-parametric Wilcoxon matched-pair signed-rank test was used to demonstrate significant differences in calf volume between two different thigh-cuff inflation pressures. The Friedman test was used to test for differences throughout the full range of inflation pressures. The Spearman rho test was used to test for significant correlations between the percentage calf volume reduction versus the compression duration and rate of venous emptying. A p value <.05 was considered significant.
Results
Subject characteristics
The records of all the 19 (14 male) consecutive healthy volunteer studies were analysed. The median (range) age was 31 (25–56) years. They were multiethnic with marked differences in height and weight. There was no evidence of venous disease on leg examination making their clinical, etiological, anatomical, pathophysiological (CEAP) 5 class as C0.
Pressure–volume relationship
With each successive increase in thigh-cuff pressure, there was a significant increase in calf volume at p < .0005 (Figures 3 and 4). The maximum increase was observed between 10 mmHg and 20 mmHg (22.2% [IQR: 17.8–24.9], p < .0005). Interestingly, a thigh-cuff pressure from 70 mmHg to 80 mmHg still caused a significant increase in calf volume (4.8% [IQR: 4.2–7.3], p < .0005). This suggests that thigh-cuff pressures ≥80 mmHg are required to occlude all veins in the leg of a supine subject. However, it is acknowledged that thigh-cuff pressure may not accurately represent deep venous pressure. This is because the tissue resistance to thigh-cuff inflation may reduce the pressure transmitted to the vein wall, especially in larger thighs.
Boxplot illustrating the calf volume in response to thigh-cuff inflation expressed as a percentage of the inflow volume. Outliers are indicated by a small circle.
Inflow and outflow volume
Calf volume changes in response to thigh-cuff compression/release in 19 subjects/legs.
IQR: interquartile range; SD: standard deviation.
As a percentage of the inflow volume (IV).
VET90: venous emptying time, this is the time taken to empty 90% of the outflow volume.
As a percentage of the outflow volume (OV).
Venous return
This was assessed using the outflow curve from the point of thigh-cuff deflation, using the VET90 and the outflow fraction (Table 1). The difference between the outflow fraction measured as a percentage of the inflow or the outflow volume was significant at 7.7% (IQR: 4.6–14.7), p < .0005. Contrary to expectation, there was no correlation between the amount of additional venous emptying versus the VET90 and outflow fraction (% of outflow volume) at r = .409, p = .082 and r = −.158, p = .519, respectively.
Venous pulsation
The sensor calf-cuff demonstrated pulsation as soon as it was applied. The amplitude of this pulse increased with the higher thigh-cuff pressures as shown in Figure 5. The median (IQR) amplitude at 10 mmHg compared to 80 mmHg was 0.052 Volts (0.038–0.067) versus 0.075 Volts (0.048–0.091), respectively (p = .003). Most of the subjects reported a subjective mild throbbing sensation of their leg at the higher inflation pressures.
Tracings from a subject at 10 mmHg thigh-cuff pressure (a) and 80 mmHg thigh-cuff pressure (b). Note the increase in the amplitude of the pulsation at the higher pressure. One small square represents 0.020 Volts vs. 0.5 s.
Discussion
This is the first study to report a counter-intuitive observation that direct thigh compression can augment the venous return and reduce calf volume. The lower volume baseline consistently recorded as part of an APG test that measures the outflow fraction is well recognised. It appears that the release of the thigh-cuff causes an initial increased rate of outflow which seems later to overshoot and empty the veins beyond usual residual volume. However, the reason why the venous emptying was greater than the arterial inflow at this point remains speculative. Since arterial pressure is usually greater than venous pressure, why should there be greater forces emptying the leg? The following explanations are proposed.
First, the reluctance to report this finding may be because it is unexpected and may be considered an artefact. A common explanation is that the pressure in the APG sensor cuff increases by the warmth radiating from the calf (Charles’ law). However, high cuff pressures occur in situations of high calf volumes and venous filling (because it presses on the cuff), rather than the observed low volume state at the final baseline. Another explanation is the loss of pressure from the system caused by stretching of the air-bag with time, termed ‘material’s creep’. However, reproducibility tests, with the sensor cuff around a rigid cylinder, have quantified this loss equivalent to 2.7 mL (range: 1.1–3.8) after 10 min constant pressure at 6 mmHg. This study therefore confirms that the majority of the volume reduction is real and proposes two explanations namely, reactive hyperaemia and the opening up of the venous outflow pathways.
Reactive hyperaemia is used commonly to test the responsiveness of the endothelium by measuring the resulting flow-mediated dilatation in peripheral arteries. 6 The mediators which are thought to play a role include nitric oxide, 7 prostaglandins, 8 ATP-dependent potassium channels 9 and adenosine. 10 Whilst thigh-cuff pressures of only 80 mmHg are insufficient to occlude arteries, as performed in a standard forearm reactive hyperaemia test of 200 mmHg for 5 min, 11 it is likely that with prolonged venous obstruction the concentrations of many of these vasoactive mediators will be increased in the leg.
The evidence that a temporary obstruction of an outflow path can augment the outflow on release is provided in the specialties of respiratory medicine and urology. The hypothesis is that an outflow resistance causes back pressure and subsequent dilatation of the outflow paths. On release, forward flow is facilitated (Figure 6). This principle is used by patients with chronic obstructive pulmonary disease to improve their breathing
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and as a test for bladder outlet obstruction.
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Schematic illustration of how thigh compression may enhance venous emptying by reducing the resistance of the microcirculation (MC). Without compression, there is a high capillary resistance (a). With venous outflow occlusion, the veins and venules dilate back to the capillaries (b). On thigh-cuff deflation, the venous outflow is enhanced temporarily from direct arterial drive-through (c).
Factors which may have influenced the net reduction in calf volume are (i) the duration of thigh compression and (ii) the rate of venous emptying. A prolonged thigh compression may have increased the accumulation of vasoactive metabolites. A rapid rate of emptying quantified by a short VET90 and a high outflow fraction may imply a greater buildup of mediators which encouraged overshoot to a lower baseline. However, none of the correlations above, when tested, were significant. The close ranges of the data may be responsible for this, and future work on patients with a wider data spread will determine whether these factors are valid.
A short duration VET90 and a high outflow fraction represent a rapid venous return provided there is no proximal obstruction to outflow. Since the inflow and outflow volumes have different values, the outflow fractions calculated from these volumes necessarily also have different values. They were significantly different in the current study. Therefore, a standard way of calculating the outflow fraction is required to ensure consistency in reporting. Until then, it is recommended that the baseline for determining the outflow fraction is selected at the end of the curve, using the outflow volume, unless stated otherwise in the method.
The general observation that the amplitude and intensity of pulsation increases at the higher thigh-cuff pressures suggests that this may be relevant in promoting the venous return in situations where the outflow is obstructed. This includes a high calf muscle pump afterload which is typical in a dependent leg at rest subjected to a high hydrostatic pressure from gravity. The calf muscle pump is similarly inactive in the supine subject and is unlikely therefore to assist in the venous return. However, any leg movement will utilise the venous muscle pumps to return blood back to the heart. The presence of venous pulsation was recognised over 50 years ago, 14 and there is increasing evidence to indicate that arterial drive-through may be responsible for this phenomenon. Although all venous return at rest is dependent on a cardiac impulse, the explanations of arteriovenous fistulae, 15 microcirculatory relaxation 16 or shunting 17 are speculative.
The high pressures (≥80 mmHg) required to prevent the supine venous return demonstrated in this study support the theory that arterial drive-through is a main contributing factor. In a study using thigh-cuffs with windows to measure the diameters of veins with ultrasound, it has been shown that local pressures of more than 40 mmHg are required to significantly reduce the diameters of the great saphenous and femoral veins whilst sitting. 18 Even pressures of 60 mmHg were unable to occlude these veins in that study. 18 The same group, using a similar technique, examined the external pressures required to occlude calf veins. 19 Complete occlusion of superficial and deep leg veins occurred at the application of 20 to 25 mmHg in the supine position, between 50 and 60 mmHg in the sitting position and at about 70 mm Hg in the standing position. 19
The current study used a pressure versus time relationship to study venous outflow in the whole leg. At each thigh-cuff inflation step of 10 mmHg, there was a corresponding increase in calf volume until a plateau was achieved. Successively increasing plateaus indicated that the thigh pressures used were unable to occlude all veins in the supine subject. Whilst the pressure required to occlude a single vein may be small, the pressure required to occlude all veins in a limb for several minutes is likely to approximate to arterial pressure.
Limitations
The main limitation is that only a single thigh compression and release manoeuvre was used to assess the net effect on calf volume in healthy volunteers. However, this was a first step to test the effects of intermittent pneumatic thigh compression. Since the concept is new, future experiments are required to determine if subsequent thigh compressions reduce calf volume further and whether these effects are maintained on patients in the long term and for how long. Patients with oedematous legs may benefit the most because there is more fluid to shift than in healthy subjects.
Conclusion
This study has demonstrated a technique of augmenting venous return using a pneumatic thigh-cuff. It has shown that in the supine subject, external pressures of 20 mmHg cause significant increases in venous volume but pressures ≥80 mmHg are required to fully occlude veins. This study is the first to report that a brief period of thigh compression to 80 mmHg caused significant physiological changes so that, on thigh-cuff deflation, the venous emptying was enhanced and the calf volume decreased significantly below baseline. Future work is required to determine the clinical significance of these findings. This will be achieved by comparing these effects on patients, evaluating the haemodynamic factors and biological mediators important for these changes and to optimise this technique as a therapeutic way of augmenting venous flow and reducing oedema.
Footnotes
Conflict of interest
None declared.
Funding
We are grateful to Ealing Hospital NHS Research & Development, Middlesex, UB1 3HW, UK who funded the study.
Ethical approval
The protocol was approved by the regional research ethical committee of London-Dulwich (REC number: 13/LO/0155).
Contributorship
CL and GG conceived and designed the study. EK and MA were involved in the recruitment of subjects, performing the tests and in the data analysis. CL and EK were involved in gaining ethical approval. CL wrote the first draft of the manuscript. All authors reviewed and edited the manuscript and approved the final version of the manuscript.