2.7 Colour duplex ultrasound imaging 2.8 The AVI footpump
One hundred and seventy seven subjects were studied in a series of seven experiments. An outline of the methods and instrumentation employed in the studies comprising this thesis is given in this chapter. Some detailed aspects of the methodology that are specific for each experiment are described in the relevant chapters.
2.1 Selection of subjects
Subjects of my studies were either patients with venous disease, attending the Middlesex Hospital Vascular Laboratory for venous assessment, or subjects with no evidence of arterial or venous disease who were either healthy volunteers solicited from members of staff at the Middlesex Hospital or inpatients at the Middlesex Hospital for unrelated conditions.
All patients included in my studies (excluding study V) had clinical lipodermatosclerosis (LDS) and proven venous insufficiency as demonstrated by colour duplex scanning. Control subjects had clinical assessment and colour duplex scanning to exclude significant venous disease. In all studies, none of the patients had open ulcers or other skin conditions such as eczema or scleroderma. All patients and control subjects had normal ankle/brachial pressure indices (ABPI > 0.9) and diabetic patients were excluded (as documented in hospital records or by urine testing). The patient group in study V comprised elderly subjects at risk of decubitus ulceration and were defined as those with a score of 14 or less, according to the Norton risk assessment scale (Norton 1975). Norton scale (Table 2.1) assesses five characteristics relating to the patient's clinical condition: The physical condition, mental state, activity, mobility and incontinence; each of these variables is graded from 1 to 4. The total score is the added values for the five components scored for the patient. The highest score '20' indicating the least risk, whereas the lowest score '5' indicating the highest risk. A score of 14 or less indicates susceptibility to pressure ulceration. Four of the patients had rheumatoid arthritis, two were being treated with steroids. No attempt was made to exclude the
possibility of small vessel disease in these rheumatoid patients. None of the patients had open heel ulcers. The results of this assessment on the patient group in this study are shown in Table 2.2.
Informed written consent was obtained from each subject and the studies were approved by the local Ethics Committee.
All studies using l a s e r Doppler fluxmetry (studies I-V) were carried out in an environment-controlled chamber (Medicin AB, Sundyberg, Germany) set at a temperature of 22°C and 30% relative humidity. The chamber was switched on for two hours before use to allow it to reach the desirable temperature and humidity and the subjects lay supine on an examination couch for an acclimatisation period of 20 minutes before any recordings were made. The two studies using strain gauge plethysmography and duplex ultrasound imaging (studies VI and VH) were also carried out in the vascular laboratory, but it was not practical to perform them in the environmental chamber.
Score 4 3 2 1
Physical condition G ood Fair Poor Very poor
Mental state A lert Apathetic Confused Stupor
Activity A m bulant W alks w ith help Chair-bound Bed-fast
Mobility Full Slightly lim ited Very limited Im m obile
Incontinence N one Occasionally Usually D oubly
Total score 20 5
Table 2.1 Pressure ulcer risk assessm ent tool (N orton Scale)
Patient W m m m : w m m m m 9 10
Physical condition poor fair poor very poor fair poor fair poor poor poor
Mental state alert alert alert alert alert apathetic apathetic alert alert alert
Activity chair bound chair bound chair bound chair bound chair bound walks - help walks - help chair-bound chair bound chair bound
Mobility very limited immobile immobile very limited immobile very limited very limited very limited very limited very limited
Incontinence occasionally usually occasionally occasionally occasionally occasionally occasionally occasionally occasionally occasionally
Norton score ■ 13 ^ ' 1 2 " ■ 12 / 13 14 .... 13
Table 2.2 Pressure ulcer risk assessm ent in the patient group using Norton score
2.2 Analysis of data
Statistical analyses w ere m ade using W ilcoxon m atched-pairs signed ranks test for paired data (for w ithin-subject differences) and M ann-W hitney U -test for unpaired data (for betw een-subjects differences); differences were considered significant if the p value w as less than 0.05. T he 95 per cent confidence intervals (95% C l) were com puted by W ilcoxon's m ethod to dem onstrate the m agnitude o f differences. The descriptors used are the m edian and interquartile range (IQR). Statistical com putation was carried out using the Statistical Package for Social Sciences (SPSS Inc. C hicago, U SA ) and C onfidence Interval A nalysis (CIA, published by the British M edical Journal, T avistock Square, London).
Calculation of the median percentage change
The m edian percentage change in the l a s e r D oppler value is defined as the increase (or decrease) in LASER D oppler value expressed as a percentage o f the resting value. It is calculated separately for each individual subject according to the form ula:
% change in l a s e r value = [(resting value - the new value) -^resting value]x 1(H)
T he ‘new valu e’ is the l a s e r D oppler value follow ing the provocation stim ulus (e.g. dependency, elevation or application o f com pression. T he m edian o f the resultant values is the m edian percentage increase (or decrease) in the LASER D oppler value. This m ethod is used to calculate the m edian percentage change in the LASER D oppler values as a result o f the veno-arteriolar response (Study I), leg elevation (Study II) and the effects o f com pression on the skin m icrocirculation (Studies III, IV &V).
In experim ents I through V, l a s e r D oppler fluxm etry was used for assessm ent o f the skin m icrocirculation. In the last tw o studies (VI and VII), strain gauge plethysm ography and duplex ultrasound im aging were used for haem odynam ic assessm ents. A brief description o f these techniques is given below.
^ U ’‘> 2 .3 La s e r D o p p le r f lu x m e t r y v f\u?tw'Y^
The principles o f this technique have been described in section 1.4.3. T he LASER
D oppler m easurem ents were m ade using a Periflux PF2 in experim ents I, II and III and Peri flux PF 2B in experim ents IV and V (Perim ed, Jarfalla, Sw eden). C alibration was perform ed using Periflux M otility Standard PFIOO solution.
Because the technique relies on the D oppler principle, w hen l a s e r light is applied to the skin, photons scattered by m oving blood cells undergo a frequency shift, w hereas photons scattered in stationary tissues rem ain unshifted. The am ount o f LASER light reflected back from the skin w ith altered frequency (D oppler-shifted light) is proportional to the volum e or concentration o f m oving blood cells in the tissues (C M B C ). The m ean frequency shift in the l a s e r light is proportional to the average speed o f m oving blood cells or blood cell velocity (BCV). The LASER D oppler flux value (LDF), w hich is proportional to the total skin blood flow in the target tissue volum e, is the product o f these two param eters (N ilsson et al. 1980a).
M ost studies investigating skin blood flow using l a s e r D oppler fluxm etry report only the LASER D oppler flux value that is related to total skin blood flow in the target tissue volum e. A nalysis o f the com ponents o f the LASER D oppler flux signal m ay provide useful inform ation as to how blood flow is altered in liposclerotic skin. The Periflux PF2 provides LASER D oppler flux (LDF) and concentration o f m oving blood cells (CM BC ) signals. The flux and C M B C signals were accessed via a 15-way ‘D ’ connector on the Perim ed m achine and fed into an analog-digital converter card on an IBM - com patible com puter. Flow data were sam pled at a rate o f 0.8 H z, corresponding to a sam pling interval o f 1.25 seconds, and stored on the com puter in a database using softw are developed by M r PD C oleridge Sm ith and D r S C hittenden. T he L D F value is proportional to total skin blood flow in the target tissue volum e. It is the product of
CMBC and blood cell velocity (BCV). By dividing the flux value by the CMBC at each point, the mean blood cell velocity was calculated.
Since the l a s e r Doppler signal is produced by moving objects (comprised largely of red blood corpuscles), stationary structures, including skin pigment and oedema, have no direct effect on the LASER Doppler signal. However, tissue properties (e.g.
hyperkeratosis and pigmentation) may result in reduced depth of flow detection and can therefore, indirectly, affect the l a s e r Doppler signal. Oedema may cause greater separation of the blood vessels, resulting in a reduction in the l a s e r Doppler signal. Despite these theoretical considerations, all studies reported in scientific literature show an increased LDF in liposclerotic skin of patients with CVI ((Belcaro et al. 1988, Cheatle et al. 1991a, Shami et al. 1993a). Because major superficial vessels influence the LASER Doppler flux reading, I ensured that the probe was not overlying a major vein.
Other factors that may affect the l a s e r Doppler output include the temperture, type of probe and haematocrit (Driessen et al. 1990).
All my studies using l a s e r Doppler fluxmetry were carried out in an environment- controlled chamber set at a constant temperature and humidity, and for any one experiment I used the same type of probe for all subjects. It has been reported that plasma viscosity, ESR and fibrinogen are increased in patients with post-thrombotic syndrome, but the haematocrit is not significantly different from control subjects (Ernst et al. 1986). Differences in l a s e r Doppler measurements between patients with CVI and control subjects cannot, therefore, be attributed to differences in haematocrit.
2.4 Experimental system for leg compression
The purpose o f the next phase (studies HI and IV), was to exam ine the effect o f leg com pression on the skin m icrocirculation using LASER D oppler fluxm etry.
A problem w ith application o f com pression to a probe is that pressures higher than
intended may be produced im m ediately beneath the probe. To avoid this problem , I ^ contained the l a s e r D oppler fibreoptic system w ithin a polythene cham ber that was
used to com press the skin under study. I was also able to verify, using an interface pressure m easuring device, that the com pression applied to the skin w as equal to the pressure in the cuff. Thus, I was confident that the cu ff pressure corresponds to the com pression applied to the skin during the study. This com pression system (Figure 2.1) consists o f a flexible angled l a s e r D oppler probe (PF 110), in its holder (PF 114), attached to the inside o f a polythene cham ber. The polythene cham ber was applied to the leg with the l a s e r beam directed onto the skin. A blood pressure c u ff was applied over the polythene cham ber. Both the blood pressure c u ff and the polythene cham ber were inflated w ith air. The reading on the sphygm om anom eter, therefore, reflects the pressure being exerted on the skin underneath the polythene cham ber, including that beneath the l a s e r D oppler probe. The com pression applied by the com bination of polythene cham ber and cuff was checked against that recorded by an interface pressure sensor (Talley Group Ltd, Rom sey, H ants UK) applied to the skin underneath the polythene cham ber; the use o f this device for interface pressure m easurem ents has previously been described in m ore detail (A bu-O w n et al. 1993b). The pressure applied to the cuff, indicated on the sphygm om anom eter, ranged from 10 to 100 m m H g and was w ithin 5 m m H g o f the pressure reading indicated by the interface pressure sensor (Figure 2.2).
Sphygm om anom eter
BP Cuff
Perimed PF2 Computer
Plastic cham ber
LASER p r o b e
Figure 2.1 D iagram m atic representation o f the experim ental m odel for leg com pression. The laser D oppler probe, installed in a polythene cham ber, is applied to the supram alleolar region underneath a blood pressure cuff. Inflating the blood pressure cuff also inflates the polythene cham ber via a Y -junction. A com puter data logging system records laser D oppler param eters from the laser D oppler fluxm eter.
Interface pressure (mmHg) 120
T
r = 0 .9 9 90 "" 60 "" 30 "• 20 40 60 0 80 100 Pressure indicated by sphygmomanometer (mmHg)Figure 2.2 Relationship between the interface pressure sensing device and the sphygmomanometer readings in ten subjects. The pressure applied to the cuff, indicated on the sphygmomanometer, ranged from 10 to 100 mmHg and was within 5 mmHg of the pressure reading indicated by the interface pressure sensor.
The next logical step would be to make direct LASER Doppler measurements from
underneath compression stockings. Such measurement was the subject of study IV; an ultra-low profile single-fibre l a s e r Doppler probe that could fit underneath a compression stocking was used so that pressures higher than intended are not produced immediately beneath the probe. After recording the resting values of LDF, BCV and CMBC with the subject in the horizontal position, a class II (Swiss Standard) graduated compression stocking, Venosan 2002 (Salzmann AG, St Gallen, Switzerland), was applied to the leg overlying the l a s e r probe and the measurements repeated. The protocol was repeated while the subject was sitting with the legs dependent. The pressure produced by the stocking was verified in situ by an interface pressure sensor (Talley Group Ltd, Romsey, Hants, UK) and was found to range from 20 to 27 mmHg.
2.5 Experimental system for compression of the heel
Since the heel is known to be at high risk of developing pressure ulceration and the effect of compression on the skin microcirculation of the heel has not been studied, this was the subject of my next experiment (study V).
The tissue loading "pressure” device (Figure 2.3): For the purpose of this study, and in conjunction with the Medical Physics Department (UCL), I designed a special device for compression of the heel. It consisted of a stand and a pivoted arm mounted on the stand. This horizontal arm could be adjusted up and down as well as sideways. A standard 5 cm diameter pressure-applying acrylic indenter with a slot to accommodate a low profile l a s e r Doppler probe was used to apply forces of 50 - 1500g to the heel region. A cantilever mechanism was used with a central pivot, so that the force could be applied to the opposite end of the arm to which the pressure indenter is attached. The pressure applied to the skin of the heel (interface pressure) was measured by the interface pressure sensor used in experiments m and IV. La s e r Doppler measurements of the skin of the heel were made using a Periflux PF 2B l a s e r Doppler fluxmeter and a
specially designed low profile l a s e r Doppler probe, PF 315:76 (Perimed, Jarfalla , Sweden).
The resting l a s e r Doppler flux was measured with the subject lying supine. Compression forces were then applied in increments from 50g to 1500g and the corresponding interface pressure (IP) and LASER Doppler flux (LDF) recorded. The IP
and LDF were also measured from the heel while the subject was lying on a low air-loss system and then on a conventional hospital bed. The detailed protocol and results of the study are presented in chapter V.
LASER
probe
Pivoted
arm
weights
loaded
here
Acrylic indenter
Computer
Perimed
PF2B
Interface pressure
sensor
Figure 2.3 Experimental system for compression of the heel. An acrylic indenter with a slot to accommodate a low profile l a s e r Doppler probe is used to compress the heel. The l a s e r Doppler fluxmeter is logged to a computer for data recording. The compression applied to the skin of the heel is measured by an interface pressure sensor.
Compression treatment is as important in DVT prophylaxis as it is in the treatment o f chronic venous insufficiency and venous ulceration. The final phase o f this thesis (studies VI and VII) is concerned with the assessment o f the haemodynamic effects o f different modalities o f compression used in DVT prophylaxis.
Intermittent pneumatic compression (IPC) has been widely used in the prophylaxis of DVT. It has also been reported recently that IPC may be useful as an adjunct to the management of patients with chronic venous insufficiency (Coleridge Smith et al. 1990a). IPC may be applied either as uniform compression to the limb, using a single chamber device or alternatively through a series of chambers inflated in a sequential manner from the ankle to the thigh to achieve venous emptying. Both these modalities of intermittent pneumatic compression are used for DVT prophylaxis. Reports of laboratory studies of hydraulic models suggested that uniform single-chamber compression could produce an occlusive tourniquet effect (Kamm 1979, Kamm 1982, Olson et al. 1982). In study VI, strain gauge plethysmography was used to compare the haemodynamic effects of sequential intermittent pneumatic compression with single chamber calf compression.
The intermittent pneumatic compression devices: Two intermittent pneumatic compression devices were used: The multi-chamber sequential device (Kendall: Kendall Healthcare Products Company, Mansfield, Massachusetts, USA), sequentially compresses the lower calf, upper calf, and thigh with 40 to 55 mmHg for 12 seconds every minute. The single-chamber (Venodyne: 1000 Highland Avenue, Needham Heights, USA) provides uniform calf compression alone; it applies 60 mmHg compression for 5 seconds once per minute.