Results from an Outpatient Conservative Treatment of 1000 Consecutive Varicose Ulcers

Results from an outpatient conservative treatment of 1000 consecutive varicose ulcers. Risk factors involved.

Bertranou EG, Gonorazky SG.

Division of Surgery and Department of Research. Hospital Privado de Comunidad de Mar del Plata. Argentina.

Presented to Journal of Wound Disease, june 2011.

ABSTRACT

Venous ulcers are non-life threatening though disabling conditions that pose a burden to patients, their family and society. Little is known about their pathologic physiology by general practitioners, and their high recurrence rate aggravates treatment problems. This work aims at retrospectively presenting the results obtained from a 17-year unchanged treatment, based only on a conservative, outpatient approach with elastocompression. This study comprises a cohort of 1,000 consecutive patients diagnosed with venous ulcer during 1990-2007. The treatment consisted in daily healing (self care) with silver sulfadiazine cream, cotton and elastic bandages. Controls for debridement were conducted every fortnight or monthly. To favour actuarial evaluation, ulcers were stratified into three groups based on their surface: A ≤10cm²; B >10≤30cm², and C>30 cm². Kaplan-Meier actuarial analysis and Cox regression technique were applied. Results: Taking into account the healing percentages corresponding to the three surfaces and 3 periods (3, 6, and 9 months), results were as follows: 3 months: A) 62% (58-66%), B) 35% (28-43%) and C) 21% (14-31%); 6 months: A) 81% (78-84%); B) 65% (58-72%); and C 41% (32-52%); 9 months: A) 87% (84-90%) B) 76%; (69-82%) and C) 52% (42-62%). The predictor variables of late ulcer closure were: ulcer surface, time of ulcer evolution and age of the patient.

Conclusions: The ulcer surface is the most important predictor variable. This study may help to compare treatment innovations and to provide a prognosis of healing time.

KEYWORDS: Varicose Ulcer, Varicose Ulcer/therapy, Cohort Studies, Actuarial Analysis, Multivariate Analysis, Outpatient Care, Risk factors.

INTRODUCTION

Venous ulcers constitute a pathology that seriously affects people’s life quality. It is estimated that 1% of the adult population suffers from this type of ulcers in their lifetime, its prevalence ranging from 0,1% to 0,3% in the population (1-3).

Our centre implemented a simple, outpatient, conservative, therapeutic program based on elastocompression and self-care. Periodic evaluations of the program were conducted and the first outcomes were published in 1992 (4).

This paper aims at presenting the results obtained from treating 1,000 patients suffering from venous ulcers between 1990 and 2007. Not only was the number of patients large, but also the research period long though the treatment remained unchanged (no new therapeutic approaches were adopted). Moreover care was provided by the same staff and in the same centre throughout the research period. All this could let us accurately estimate healing time as well as the risk factors associated with this pathology, based on the supposition that the population was representative of the general population.

MATERIAL AND METHODS

The study was carried out in the Phlebology Service of the Hospital Privado de Comunidad de Mar del Plata between 1990 and 2007. One thousand patients with venous ulcers due to superficial and/or deep vein failure after deep vein thrombosis were prospectively included. Peripheral arterial circulation was good in all these patients.

Data and variables were stored in a database of the service created to such end.

The conservative and outpatient treatment was based on the patient’s and family’s education on self-care and elastocompression. Treatment was initiated after the clinical diagnosis of venous ulcer and after verifying the presence of palpable peripheral pulses (the ankle brachial index pressure was 0,7 or more). Ulcers size was calculated by multiplying their two maximal perpendicular diameters (5). For control purposes, ulcers were photographed afterwards and stored in the database. Deep debridement of the ulcer was carried out with local anesthetics, and the patient and family were educated regarding wound healing, thereby encouraging self-care. Wound care comprised applying moisturizer cream around the ulcer, then silver sulfadiazine-lidocaine cream. Afterwards sterile dressings and gauze bandages were placed over the wound. Healing was completed with an elastic bandage of rubber filaments. Bandage pressure at the forefoot and ankle was of approximately 60 mmHg so as not to hinder arterial circulation, of 40 mmHg at the mid leg segment, and of 20 mmHg below the knee, thereby favouring venous return through the perforators (i.e., the saphenous and posterior arch veins) toward the deep veins (6). The Service used a device with an inflatable rubber end, calibrated with a mercury manometer, which measured the bandage approximate pressure. The didactic aim was that of teaching patients how to apply the bandage. A brochure with key information and advice on eating without salt and taking regular walks, among others, was handed in. Next visit was after one week, and then errors in the healing process were corrected. Surgical debridement was performed with topical anesthetics, and an appointment was scheduled for a meeting in a fortnight or month until ulcer closure.

Data were stored in the database during the diagnosis and during the patient’s evolution.

Time was analyzed on ulcer closure. Independent variables were: ulcer size at the moment of the first visit stratified into three groups: A ≤10cm²; B >10≤30cm², and C>30 cm², time of ulcer evolution (by asking the patient), age, gender and history of diabetes.

If a patient presented ulcers on both lower limbs, the largest one, or that appearing in the first place, was analyzed.

If relapse occurred, just the primary ulcer was analyzed.

STATISTICS

Descriptive (median, interquartile range and range) Kaplan-Meier actuarial analysis and Cox regression technique were applied. Variables with statistical significance in the univariable analysis less than or equal to 0,15 were included in the multivariable analysis. Said analysis was conducted in conformity with the stepwise method of conditional regression (SPSS 11.5.1).

RESULTS

The period analyzed allowed us to include 1,000 patients (Table 1). Median age was 70 years (24 to 95 years). Sixty five percent were women, and the median ulcer surface was of 4,7 cm². Thirteen percent suffered from diabetes, and the first visit upon ulcer occurrence had been after a median of 3 months (0,5 to 488 months) (Table 1).

Median time until healing was of 2,6 months (95% CI, 2,6 to 3 months).

Statistically significant independent variables (risk factors) were: age, time elapsed until the first visit (ulcer age) and ulcer size. The first three variables prolonged healing time in a directly proportional way.

The ulcer size was the most relevant clinical feature (Hazard Ratio in the multivariate analysis was of 0,98, 95% CI, 0,98-0,99).

Ulcers were stratified into three groups based on their surface: A: smaller or equal to 10cm²; B: larger than 10 though smaller than 30cm², and C: larger than 30 cm² (66%, 20% and 14% of patients, respectively). In this case, the hazard ratio in the multivariate analysis was of 0,66 (95% CI, 0,58-0,74) (see Table 2). Median time on ulcer closing was of 2,3 months, respectively (95% CI, 2,2-2,5 months), 4 months (95% CI, 3,1-5,2 months), and 8 months (95% CI, 3,1-5,2 months) (Figures 1 and Table 3).

Table 1

Number of Patients: 1000

Females: 653

Age of females: 71 years (M); 63 - 77 years (IR); 32 - 95 years (R)

Males: 347

Age of males: 69 years (M); 61 - 75 years (IR); 24 - 93 years (R)

Surface of primary ulcer: 4,7 cm² (M); 1,6 - 14,1 cm² (IR); 0,5 - 942,4 cm² (R)

TEU (time of ulcer evolution) 3 months (M); 1-3 months (IR); 0,5 - 488 (R)

Diabetes: 128 patients (12,8 %)

Follow-up: 2,3 (M); 1 - 5 months (IR); 0 - 58,2 months (R)

M: Median

IR: Interquartile range

R: Range

TEU: Time of ulcer evolution (Period between ulcer onset and first visit)

Table 2

Predictor variables of ulcer closure (<1 late closure)

Univariate Analysis Multivariate Analysis

Factors RR* (95% CI)** p RR* (95% CI) p

Age 0,99 (0,99-1) 0,08 0,99 (0,99-1) 0,04

Gender*** 1,03 (0,89-1,2) 0,18 NS

Surface**** 0,66 (0,54-0,63) 0,005 0,66 (0,59-0,75) <0,005

TEU ***** 0,99 (0,88-0,89) 0,05 0,99 (0,990-0,997) <0,005

Diabetes 0,86 (0,69-1,06) 0,16 NS

*RR= Relative risk

** 95% CI= 95% Confidence interval

*** Gender = Male

**** Surface stratified into three groups (E1≤10 cm²; E2>10≤30 cm²; E3>30 cm²)

***** TEU: Time of ulcer evolution (Period between ulcer onset and first visit)

Figure 1:

Table 3

Percentage of healed patients in different periods within one year in the three stratified groups based on size

(*) 95% Confidence interval

DISCUSSION

Our series characterizes for having a large number of patients, a long follow-up period and for having continued the same treatment during 17 years. This allowed us to determine the risk factors involved in the prognosis and to estimate probable time of venous ulcers closure, based on their surface.

Ever since the classic work by Moffat (9), which reported the results from 475 patients coming from 6 community clinics from the London area with results based on actuarial techniques, no other work has been published in the literature in this respect. As the researcher stated “ulcer treatment is rarely based on scientific principles but rather on the market forces determining the healing process, without taking into account their efficiency.”

A review of the latest bibliography (including a meta analysis of the Cochrane system) shows research works resulting from double blind trials of small series of randomized patients. All these studies include elastocompression as their mainstay of treatment, and report, in their conclusion, either improvement or progress in ulcer closure within a few months (10-20). Several therapeutic approaches are tested (physical and/or pharmacological), and just by reading the works title, it is possible to get a gist of their variety. For instance, their conclusions read: Topical autologous platelets do not show a significant adjuvant effect (10); laser does not stimulate ulcers healing (11); its is uncertain whether intermittent pneumatic compression hastens healing (12); no evidence supports the fact that antibiotics promote ulcer healing (13); the use of hyperbaric oxygen is not supported by this revision (14); the results of administering pentoxifiline orally, in spite of the evidence, should be interpreted with caution(15); the use of ultrasound should be carefully interpreted (16); no significant evidence supports the fact that honey increases ulcers healing (17); topical hidrocoloids are not significant adjuvants for ulcer closure (18); isosorbide dinitrate yielded the best results, but only during the first 6 weeks of treatment (19).

Just one work demonstrated effectiveness (20). It was a randomized study conducted with 82 patients on the use of isolated compression or ameloginin (a protein of the extracellular matrix protein family) addition. In this work, the group with ameloginin achieved a significant reduction in ulcer surface. The applicability of the method and cost-effectiveness of this approach remain to be ascertained.

The results obtained from this series should be compared to those from some relatively similar works including large number of patients (multi-centric studies) and with ulcer closure as their outcome. Both works demonstrate the action of the purified micronized flavonoid fraction. The first one, (21), is a double blind study carried out on 140 patients with >3cm² ulcers treated for 6 months. Patients treated with the aforementioned product achieved a 71% closure, while our series yielded 80% closure for >10cm² ulcers during the same period (see Figure 1). The second work, (22), performed on 107 patients with < 10 cm² ulcers, achieved 32% closure after 2 months of treatment with said product, while in our series, including 662 patients with ulcers of up to 10 cm², a 40 % closure was attained with the conventional treatment during that same period (see Figure 1).

From the above stated, it can be concluded that there is enough scientific evidence supporting that: a) for venous ulcers treatment, the use of a hemodynamic method carried out by professionals versed in vascular patophysiology based on elastocompression (saphenous and posterior arch veins and perforators) with elastic bandage is recommended; b) there are several healing products, but the scientific evidence justifying their use is weak, probably because the series are truly small; c) “adjuvants” do little more than increase the cost-benefit equation. Treatment cost and the high frequency of relapse is worth analizing in this type of ulcers.

CONCLUSIONS

The multivariate analysis shows that ulcers size, TEU (time of ulcer evolution) and patient’s age are statistically significant predictors of ulcer closure time, being ulcer size the most important clinical factor.

This study could serve as a platform to compare innovations in ulcer treatment and to offer a prognosis of patients healing time.

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