Anatomic and physiologic characteristics of venous ulceration

Anatomic and physiologic characteristics of venous ulceration A n d r e M. van Rij, M D , Clive S o l o m o n , MB, ChB, and Ross Christie, N Z C S , Dunedin, New Zealand

Purpose: The purpose of this study was to describe the combination of physiologic and anatomic changes present in limbs with venous ulceration. Methods: Limbs with venous ulceration (chronic venous insufficiency [CVI] class 3) were assessed prospectively by air plethysmography and color-flow duplex scanning. Findings were compared with clinically normal contralateral limbs and normal control limbs (CVI class 0), as well as with limbs without skin changes (CVI class 1). Results: Of the 120 ulcerated limbs studied, only 28% had deep system incompetence. Reflux at the saphenofemoral or saphenopopliteal junctions without perforator incompetence was present in 40%. Raised venous filling indexes (> 2 ml/s) and high residual volume fractions ( > 20%) were present in 90o/0 and 95%, respectively. Although levels of these parameters were significantly different from the other groups (p < 0.05), absolute ejection volumes and outflow parameters were the same (p > 0.05). One third of contralateral "normal" limbs (class 0) had abnormal duplex scanning findings. The ratio of venous filling time to residual volume fraction produced a useful discriminating index for the ulcerated limb. Conclusion: The ulcerated limb was characterized by high rates of reflux and high residual volumes that were independent of the site of reflux. This study highlights the important association of venous ulceration and isolated superficial venous system incompetence. (J VASC SURG 1994;20:759-64.)

Despite the fact that lower limb venous ulceration is a common, chronic, and costly disease, 1 modalities and efficacy o f treatment have changed little since the compression dressings o f Ambrois Par& 2 This lack of significant advancement in ulcer treatment and prevention can be linked to difficulties in assessing venous hemodynamics and to the lack o f adequate safe and accurate noninvasive tests o f venous function. Although many studies have been performed that assess the potential role o f drugs, compression devices, or surgical procedures in ulcer healing, 1,s,4 few o f these have made use o f effective methods to characterize the underlying venous hemodynamics; much reliance has been placed on tourniquet testing From the Department of Surgery, University of Otago Medical School, Dunedin. Supported by a grant from the Health Research Council of New Zealand. Presented at the Sixth Annual Meeting of the AmericanVenous Forum, Wailea, Maui, Hawaii, Feb. 23-25, 1994. Reprint requests: AndreM. van Rij, MD, Department of Surgery, University of Otago Medical School, P.O. Box 913, Dunedin, New Zealand. Copyright © 1994 by The Society for Vascular Surgery and International Societyfor CardiovascularSurgery,North American Chapter. 0741-5214/94/$3.00 + 0 24/6/58915

or examination by use o f continuous-wave Doppler scanning. Air plethysmography 5 has significantly increased our ability to measure aspects of venous and calf pump function that were hitherto unavailable with photoplethysmography. Duplex scanning, especially with color-flow imaging, has allowed accurate description o f anatomic sites o f venous disease in terms o f flow, reflux and intraluminal or extraluminal obstruction. The purpose o f this study was to describe the underlying physiologic and anatomic changes to venous function that occur in ulcerated limbs and contrast these with clinically normal limbs and those with varicose veins without skin changes. In this way it was intended to gain better definition o f the ulcerated and at-risk limb by noninvasive physiologic tests and imaging. This has implications in optimizing patient selection and the choice o f operative procedure for both healing and preventing venous ulceration.

METHODS Patients for the study were recruited from the Vascular Assessment Unit of the University o f Otago 759

JOURNALOF VASCULARSURGERY 760 van Rij, Solomon, and Christie

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Table I. Physiologic parameters as means _+ SD for group I (ulcers), group II (varicose veins), group III (contralateral normal limbs), group IV (controls) VFT* VFIq: (ml/sec) RF]VV:~ (ml) EF# RV$ (ml) EV (ml) 2-second outflow ratio Maximalvenous outflow (ml/sec)

Group I (n = 120)

Group 17 (n = 70)

Group 117 (n = 85)

Group I V (n = 20)

36 ± 19 4.6 ± 2.7 0.51 ± 0.17 128 ± 58 0.50 ± 0.20 68 ± 41 63 ± 30 0.64 ± 0.16 43 _+ 18

78 -+ 48 3.0 -+ 2.9 0.43 ± 0.19 139 + 55 0.53 ± 0.I8 62 ± 38 70 ± 32 0.67 ± 0.18 47± 18

119 ± 59 1.3 ± 1.3 0.33 -~ 0.18 108 ± 41 0.65 ± 0.18 37± 24 69 ± 3I 0.70 ± 0.21 46± 16

202 ± 71 0.5 -+ 0.2 0.29 ± 0.14 94 ± 42 0.65 ± 0.14 26± 20 60+_29 0.69 ± 0.14 45 ± 17

*Significantdifferencebetween all groups. tSignificantdifferencebetween all groups exceptIII and IV. $Significantdifferenceof I and II from III and IV. p < 0.05. and assessed clinically. Limbs were divided into three groups: I, venous ulceration; II, varicose veins without skin changes; III, clinically normal contralateral limbs. A fourth group of controls included limbs that had no history, clinical evidence, or duplex scanning-detected signs of venous disease. Groups I and II correspond to the Society for Vascular Surgery/International Society for Cardiovascular Surgery (SVSflSCVS) dasses 3 and 1, respectively. Groups III and IV are subgroups of SVS/ISCVS group 0. 6 Patients were excluded if they had significant lower limb arterial disease (anlde-brachial index [ABI] < 0.8), mobility problems precluding physiologic testing, or features suggestive of a nonvenous cause of ulceration. Limbs that did not clearly meet the criteria for indusion into one of the four study groups were excluded. These included limbs with significant arterial disease, lymphedema, varicose veins with skin changes but no ulceration (CVI/ISCVS class 2), cellulitis, symptoms of swelling, or pain not clearly related to the venous system. All subjects gave consent for the study, which had received ethical committee approval. Physiologic testing. Air plethysmographys was performed on each limb with use of a computerbased MacLab/8 multi-channel recording system (Analog Digital Instruments, Dunedin, New Zealand) on an Apple Macintosh Quadra 800 (Apple Computer Corp., Cupertino, Calif.). Venous filling time (VFT), venous filling index (VFI), venous volume (VV) (ml), ejection volume (EV) (ml), ejection fraction (EF), residual volume (RV) (ml), and residual fraction (RF) were measured. A further ratio of VFT to residual volume fraction was calculated. This relates the degree of reflux to ambulatory calf muscle function and was assessed as a possible predictor of venous ulceration. Outflow capacitance

(ml), maximum venous outflow (ml/sec), and the 2-second outflow ratio were calculated after release of a 20 cm thigh cuff inflated to 50 m m H g until maximal venous filling had occurred. Outflow studies were performed with the patient in the supine position and with the leg elevated to 20 degrees in a stirrup. Duplex scanning. After the physiologic assessments, color-flow duplex imaging was performed on each limb with an Acuson 128XP/5 scanner (Acuson, Inc., Mountain View, Calif.). A 7 M H z 3 8 m m linear probe was used routinely. A 5 M H z linear probe was used when adipose tissue in the thigh prevented adequate visualization of vessels. Pulsed-wave and color-flow Doppler imaging frequencies for file two probes were 5 M H z and 3.5 MHz, respectively. Imaging of the thigh veins was performed with the patient in the supine position and at 30 degrees reverse Trendelenburg and with the patient sitting up for examination of the popliteal and calf veins. 7 All sites of abnormal flow (reflux or obstruction) were documented with particular exclusion of abnormalities at the saphenofemoral and saphenopopliteal junctions, perforators, and deep veins. Reflux was determined by the presence of retrograde flow either during sustained Valsalva or after augmentation of flow by a standardized calf compression to 100 m m H g with an automated release 10 cm oaffjust below the level of the tibial tuberosity. Perforator incompetence was defined as bidirectional flow elicited either by manual compression or Valsalva. All vein segments were scanned from internal iliac to the distal calf veins including assessment of vessels within the ulcer bed. Statistical methods. Statistical analysis was performed with SPSS (Statistical Package in the Social Sciences, Chicago, Ill.) on a Macintosh Quadra 800

JOURNAL OF VASCULAR SURGERY Volume 20, Number 5

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(Apple Computer Co.). Nonnormally distributed parameters were log transformed before statistical tests. Analysis of variance with Duncan's multiple range test was used to distinguish significant group differences. Cumulative percentage frequency plots were calculated for each of the parameters by clinical group. The VFI and VFT/RF ratio was further analyzed for the ulcer group on the basis of the duplex scanning-detected abnormality. Chi-squared tests were used for frequency analyses of duplex findings between groups. The level of declaring statistical significance was set at 0.05. RESULTS Physiologic tests. Two hundred ninety-five limbs of 210 patients were included in the study. Group I (ulcers) comprised 120 limbs, group II (varicose veins) 70 limbs, group III (contralateral normal limbs) 85 limbs, and group IV (normal control limbs) 20 limbs. Mean age ( +_SD) was greater in the ulcer group compared with varicose veins and contralateral normals (61 + 14, 47 _+ 16, 49 _+ 12, respectively). The age of control group (56 _+ 14) was not statistically different from any of the others. Physiologic parameters for the groups are shown in Table I. VFT, VFI, and RF were different in ulcerated limbs, limbs with varicose vein, and normal limbs. W , EF, and RV distinguished normal limbs from those with venous disease but did not distinguish between ulcerated limbs and limbs with varicose veins. Absolute EV and parameters of

outflow were similar in all groups. Substantial overlap in all these parameters did not allow for easy separation of the groups or definition of the diseased or at-risk limb on the basis of a single threshold value. Although some separation of the groups occurs, high sensitivity for ulcers is associated with relatively poor specificity. The ratio of VFT and RF was calculated because it combined the two most discriminating physiologic parameters. This ratio when log transformed was significantly different for all groups (2 < 0.001). Overlap was found to be minimal, and very obvious separation of groups on a cumulative percentage frequency plot was apparent (Fig. 1). A ratio of 125 was found to be the optimal cutoff. Values for this ratio below 120 include 86% of ulcerated limbs, 35% of limbs with varicose veins, 18% of contralateral clinically normal limbs and exclude all control limbs. Increasing this threshold decreases specificitywithout a notable increase in sensitivity. No normal limb (group IV) had a value below 200. The cumulative frequency plot for VFT alone shows a similar distribution and discriminating power for the ulcerated limb without taking into account calf muscle pump function as measured by RV. Anatomic description. The overall distribution of reflux in limbs is shown in Fig. 2. Group I (ulcers) had reflux detectable on duplex examination in all but one patient. In 72% of ulcerated limbs no reflux was detected in the deep system, and reflux was limited to the saphenofemoral junction, the saphenopopliteal

IOURNAL OF VASCULAR SURGERY November 1994

762 van Rij; Solomon, and Christie

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junction, or perforators. Only 28% had a component of deep reflux, and most of these limbs (71%) had superficial system involvement as well. Group II limbs had reflux in all but one patient. Deep reflux was seen in 8% of these, which was significantly less than in the ulcer group. The most common abnormality of varicose vein limbs was reflux at the saphenofemoral junction (40%). Only 68% of clinical normal contralateral limbs had normal results on duplex scanning, 27% revealed incompetence limited to the superficial system, with 5% having a component of deep system involvement. The control group by definition had no duplex scanning-detected abnormalities. Fig. 3 shows the detailed distribution of reflux in the ulcerated limbs. Anatomic and physiologic relationship. No specific site or combination of sites of reflux were characteristically associated with ulceration, and the extent of the physiologic abnormality was independent of the site of reflux. The VFT and the ratio of VFT/RF were low in ulcerated limbs, and both were independent of the specific site of reflux. Fig. 4 indicates the similar levels of reflux present in superficial and deep venous disease. DISCUSSION The results of this study highlight a number of issues that are becoming important in the modern

understanding of venous ulceration and have implications for the assessment, treatment, and screening for this disorder. Physiologic parameters indicative of high degrees of reflux have been shown, as previously noted, to be strongly associated with ulcers. Calf muscle pump function did not appear to be as important a factor as expected. The fact that absolute EV of the pump as measured during a single toe stand was not altered and that outflow parameters were normal indicate strongly that primary pump failure and outflow obstruction are of little importance in most patients with venous ulcers. The relationship between reflux and pump function is less clear. It is possible that high degrees of reflux exceed the ability of a normal pump, which in effect becomes overloaded. This is not dissimilar to the effect of incompetence in heart valves. Reflux at any site has the potential to predispose the limb to ulceration. It seems that a critical point is reached when the degree of reflux exceeds the relatively fixed EV of the calf and preload type pump failure occurs. The VFT/RF ratio attempts to quantify the effect of this phenomenon. Because EV are similar in all groups, primary pump failure does not seem to be a common phenomenon. Duplex findings confirm the importance of superficial venous disease in ulcerated limbs, the relatively infrequent finding of deep reflux, and the variable combinations of sites of reflux in ulcerated

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correction with relatively simple surgery. Postoperative physiologic testing can then be performed to ensure that an adequate elevation of the ulcer index has occurred and that the underlying abnormality has indeed been dealt with. l°

IOURNAL OF VASCULAR SURGERY

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van P~j, Solomon, and Christie

The p r o p o r t i o n o f varicose veins that fall outside o f normal physiologic parameters, are assumed but n o t proved to be those at risk for ulcer development. T h e high percentage o f these in this study m a y be a reflection o f selection bias by recruiting subjects f r o m those referred for vascular laboratory assessment. This sample m a y n o t be truly representative o f varicose vein patients in the general population. The contralateral n o r m a l limb in patients with either varicose veins or ulceration was n o t infrequently f o u n d to have duplex abnormalities, and a percentage o f these limbs w o u l d be considered to be at risk on the basis o f a low VFT. T h e y cannot therefore be regarded as a true control group. A clinical implication o f this is that apparently normal contralateral limbs o f patients with venous disease will n o t infrequently also have a degree o f venous abnormality. N e w e r m e t h o d s o f investigating patients with venous disease have increased o u r understanding o f the pathophysiologic processes involved and are tending to redirect o u r treatment protocols. These should ensure accurate diagnoses and well-planned surgical procedures where appropriate and confirm the correction o f the underlying disease. T h e clinical benefits o f this approach, for example, reduced recurrence o f varicose veins, increased ulcer healing

November 1994

and detecting and preventing ulceration in the at risk limb, will need to be proved if the time and expense is to be justified in clinical practice. REFERENCES

1. Hume M. Venous ulcers, the vascular surgeon, and the Medicare budget. J VAse SUnG 1992;16:671-3. 2. Packard FR. The fife and times of Ambrose Pard. New York: Patti B. Hoeber, 1921:232. 3. Anderson MN, Donald KE. Results of surgical therapy of severe stasis ulceration of the legs. Ann Surg 1963; 157:281-6. 4. Cotgan M-P, Dormandy JA, Jones PW, et al. OxpentifyLline treatment of venous ulcers of the leg. BMJ 1990;300:972-5. 5. Christopoulos DG, Nicolaides AN, Szendro G, et al. Airplethysmography and the effects of elastic compression on venous haemodynamics of the leg. J VAsc SURG1987;5:14859. 6. Reporting standards in venous disease. J Vasc SUV,G 1988; 8:172-81. 7. Kalodiki E, Calahoras L, Nicolaides AN. Make it easy: duplex examination of the venous system. Phlebology 1993;8:17-21. 8. Shami SK, Sarin S, Cheatle TR, et al. Venous ulcers and the superficial venous system. J VAsc SURG1993;17:487-9. 9. Hanrahan LM, Araki CT, Rodriguez AA, et al. Distribution of valxatlar incompetence in patients with venous stasis ulceration. J VASCSURG 1991;13:805-12. 10. Nicolaides AN, Hussein MK, Szendro G, et al. The relation of venous ulceration with ambulatory venous pressure measurements. J VASCSURG1993;17:414-9. Submitted March 2, 1994; accepted June 30, 1994.

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