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Eur J Cardiothorac Surg 2004;26:1015-1026
© 2004 Elsevier Science NL
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Department of Cardiothoracic Surgery, Imperial College of Science, Technology and Medicine, The National Heart and Lung Institute, St Mary's Hospital London, 70 St Olaf's Road, Fulham, London SW6 7DN, UK
Received 17 May 2004; received in revised form 18 June 2004; accepted 2 July 2004.
* Corresponding author. Tel.: +44-207-886-1147; fax: +44-207-886-1763. (E-mail: tathan5253{at}aol.com).
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Abstract |
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 Top Abstract 1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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1. Introduction |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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In a recent meta-analysis of randomised trials comparing leg wound infection rates between the two techniques, we have shown a significant reduction in post-operative wound infection with MIVH [3]. What remains to be seen is whether the minimally invasive technique also reduces the incidence of non-infective wound healing disturbances (NIWHD). These include wound drainage, haematoma, dehiscence, necrosis, need for surgical debridement, and seroma formation. The morbidity that results from these not only leads to increasing re-intervention rates and treatment costs, but also ultimately results in impaired mobilisation, increased pain, and patient dissatisfaction. This can in turn potentially result in an increased length of hospital stay.
Although several groups have tried to compare the two techniques with regards to NIWHD, it has thus far been difficult to draw conclusions from their results because of a small sample size and more importantly because of the heterogeneity in NIWHD definitions between the studies [4–6]. There are other factors that are also responsible for the significant variation in the incidence of NIWHD between different studies namely: study characteristics (design, sample size, matching, inclusion, and exclusion criteria), patient characteristics (risk factor distribution), associated procedures, equipment used, the learning curve associated with MIVH, length of patient follow-up, and finally the assessment of outcome.
This study aims to use meta-analytic techniques to compare MIVH and CVH techniques with regards to NIWHD. Meta-analysis is a useful statistical tool that can be used to evaluate the existing literature in a qualitative and quantitative way by comparing and integrating the results of different studies, taking into account variations in characteristics that can influence the overall estimate of the outcome of interest. In this meta-analysis, we are particularly interested in answering the following questions:
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2. Materials and methods |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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2.2. Data extraction
Two reviewers (A.T and A.O), independently extracted the following data from each study: first author, year of publication, study population characteristics, study design, inclusion and exclusion criteria, number of subjects operated on with each technique, time of follow-up, and conversion rate from MIVH to CVH.
2.3. Inclusion criteria
In order to enter our analysis, studies had to:
The non-endoscopic techniques included in the MIVH group used three types of instrument modification: (a) Mini-Harvest System (Autosuture; USSC, Norwalk, CT); (b) SaphLITE System (Genzyme Surgical Products, Cambridge, MA); (c) Aesculap Retractor (Aesculap AGCoKG, Tutligen, Germany).
2.4. Exclusion criteria
The following criteria were used to exclude studies from our analysis:
2.5. Outcomes of interest and definitions
MIVH and CVH were compared with regards to six types of NIWHDs as outcomes of interest, namely haematoma, oedema, skin necrosis, seroma, dehiscence, and wound drainage. In addition to the NIWHDs mentioned above, we were also interested in the length of stay (LOS) following MIVH versus CVH techniques.
2.6. Statistical analysis
Meta-analysis was performed in line with recommendations from the Cochrane Collaboration and the Quality of Reporting of Meta-analyses (QUORUM) guidelines [7,8]. Statistical analysis for categorical variables was carried out using the odds ratio as the summary statistic. This ratio represents the odds of an adverse event occurring in the treatment (MIVH) group compared with the reference (CVH) group. An odds ratio of less than one favours the treatment group, and the point estimate of the odds ratio is considered statistically significant at the P<0.05 level if the 95% confidence interval does not include the value one.
Aggregation of the overall rates of the outcomes of interest was performed with the Mantel–Haenszel Chi-square test. Yate's correction was used for those studies that contained a zero in one cell for the number of events of interest in one of the two groups [9,10]. These ‘zero cells’ create problems with the computation of ratio measure and its standard error of the treatment effect. This was resolved by adding the value 0.5 in each cell of the 2x2 table for the study in question, and if there were no events for both MIVH and CVH groups the study was discarded from the meta-analysis.
In this study we used both fixed and random effect models. In a fixed effect model it is assumed that the treatment effect in each study is the same, whereas in a random effect model it is assumed that there is variation between studies and the calculated odds ratio thus has a more conservative value [11,12]. In surgical research, meta-analysis using the random effect model is preferable particularly because patients that are operated on in different centres have varying risk profiles and selection criteria for each surgical technique.
In the tabulation of our results (Fig. 1), squares indicate point estimates of treatment effect (odds ratio), with the size of the square representing the weight attributed to each study and 95% confidence intervals indicated by horizontal bars. The diamond represents the summary odds ratio from the pooled studies with 95% confidence intervals.
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Three strategies were employed to quantitatively assess heterogeneity. First, data was re-analysed using both random and fixed effect models. Second, graphical exploration with funnel plots was used to evaluate publication bias [11,13]. Third, sensitivity analysis was undertaken using subgroup analysis. In order to do this, the following variables were evaluated:
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2.7. Sample size considerations
The overall incidence of wound healing disturbances between studies in the CVH was 520/5979 (9%). In order to rule out a 50% relative risk reduction (from 9 to 4.5%) with a 5% significance level and 80% power, we calculated that a traditional randomised controlled trial would require 531 patients in each arm.
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3. Results |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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The characteristics of these 27 studies are demonstrated in Table 1. Thirteen studies contained groups that were fully matched according to the criteria of age, sex, diabetes, obesity, and peripheral vascular disease. Twelve studies were randomised, with 25 giving results specifically for endoscopic great saphenous vein harvest (as opposed to non-endoscopic techniques). Seventeen studies contained a 50 or more patients in each of the MIVH and CVH groups, and in 21 studies the patients were undergoing GSV harvest for CABG only. All but three of the studies clearly excluded re-do operations. Finally, a conversion rate was reported in 16 out of the 27 studies (range 0–31%). The results from meta-analysis of the studies with regard to individual NIWHDs are summarised below, with Fig. 1 showing in detail the meta-analytic outcome when only the 12 randomised studies were considered.
3.2. Meta-analysis of haematoma results
Overall, 22 of the studies reported the incidence of post-operative haematoma [4–6,15–26,28–33,37], with seven of these showing a statistically significant reduction in the MIVH as compared to the CVH group. Eleven of the studies were randomised [4–6,15–22], with meta-analysis of these calculating an incidence of haematoma of 53/676 (8%) in MIVH and 93/610 (15%) in CVH groups, with an odds ratio (OR) of 0.43 and confidence interval (CI) of 0.23–0.79, suggesting that this difference is statistically significant. When considering 12 studies that were fully matched for the patient criteria previously mentioned [4–6,15,16,18,19,21–23,32,33], these results were reproduced, with an incidence of haematoma of 50/840 (5%) with MIVH as compared to 88/764 (11%) with CVH (OR 0.46, CI 0.23–0.92). The ARR in the MIVH in comparison to the CVH group was calculated to be 0.08 which can be translated in a number of patients needed to treat of 13.
3.3. Meta-analysis of oedema results
Eight studies reported the incidence of post-operative oedema [4,16,21,25,30,32,33,37], with six of these showing a statistically significant reduction with MIVH as compared to the CVH group. Only three of these studies were randomised [4,16,21], with meta-analysis showing a significant reduction in oedema between MIVH (7/90) and CVH groups (30/60) with an odds ratio of 0.06 (CI 0.01–0.36). Considering the five fully matched studies [4,16,21,32,33], also demonstrated a significant reduction in the incidence of oedema with MIVH 16/238 (7%) as compared to CVH groups 58/212 (27%) with an odds ratio of 0.10 (CI 0.02–0.59). The ARR in the MIVH in comparison to the CVH group was calculated to be 0.43 which can be translated in a number of patients needed to treat of 2.
3.4. Meta-analysis of skin necrosis results
Thirteen studies reported post-operative skin necrosis [4,5,16,20–22,24,26,27,29,32,33,37], with two of these showing a statistically significant reduction with MIVH as compared to the CVH group. Six studies were randomised [4,5,16,20–22], with meta-analysis of these showing a significant reduction in skin necrosis rates ranging from 3/326 (0.9%) with MIVH versus 23/275 (8%) with CVH groups with OR 0.15 (CI 0.05–0.43). Analysis of the seven fully matched studies [4,5,16,21,22,32,33], demonstrated an incidence of skin necrosis of 12/453 (3%) with MIVH versus 44/407 (11%) with CVH (OR 0.29, CI 0.10–0.82). The ARR in the MIVH in comparison to the CVH group was calculated to be 0.43 which can be translated in a number of patients needed to treat of 13.
3.5. Meta-analysis of dehiscence/separation results
Dehiscence/separation was reported in 12 studies [4,5,14,16,20–24,32,33,35], with three of these showing a statistically significant reduction with MIVH as compared to the CVH group. Seven studies were randomised [4,5,14,16,20–22], with meta-analysis of these showing a significant reduction in dehiscence/separation with MIVH (6/398=1%) compared to the CVH group (35/347=10%), OR 0.22 (CI 0.06–0.97). Analysis of the nine fully matched studies [4,5,14,16,21–23,32,33], demonstrated an incidence of dehiscence/separation of 7/622 (1%) with MIVH versus 50/561 (8%) with CVH, OR 0.18(CI 0.06–0.54). The ARR in the MIVH in comparison to the CVH group was calculated to be 0.08 which can be translated in a number of patients needed to treat of 13.
3.6. Meta-analysis of wound drainage results
Wound drainage was reported in 11 studies [5,15,19–23,25,26,32,36], with two of these showing a statistically significant reduction with MIVH as compared to the CVH group. Six studies were randomised [5,15,19–22], with meta-analysis of these showing a significant reduction in wound drainage between MIVH (7/393=1%) and CVH groups (29/355=8%), OR 0.24 (CI 0.11–0.54). Analysis of the seven fully matched studies [5,15,19,21–23,32], demonstrated an incidence of wound drainage of 8/600 (1%) with MIVH versus 36/444 (8%) with CVH, OR 0.20 (CI 0.09–0.43). The ARR in the MIVH in comparison to the CVH group was calculated to be 0.08 which can be translated in a number of patients needed to treat of 13.
3.7. Meta-analysis of seroma/lymphocele results
This was reported in seven studies [21–24,28,33,34], with two of these showing a statistically significant reduction with MIVH as compared to the CVH group. Two studies were randomised [21,22], with meta-analysis of these showing a significant reduction in seroma/lymphocele between MIVH 1/81 (1%) and CVH groups 12/88 (14%), OR 0.05 (CI 0.01–0.43). Analysis of the four fully matched studies [21–23,33], did not demonstrate a statistically significant reduction in the incidence of seroma/lymphocele of 8/267 (2%) with MIVH versus 19/315 (6%) with CVH, OR 0.40 (CI 0.06–2.62).
3.8. Meta-analysis of overall NIWHDs
When considering only randomised studies, the total number of NIWHDs was lower in MIVH 77/1964 (4%) as compared to CVH 222/1735 (13%), with random effect OR 0.24 (CI 0.16–0.38). This was also true when only fully matched studies were considered with 101/3020 (3%) NIWHDs in the MIVH group versus 295/2703 (11%) with CVH (random effect OR 0.28, CI 0.18–0.42). The ARR in the MIVH in comparison to the CVH group was calculated to be 0.10 which can be translated in a number of patients needed to treat of 10.
3.9. Length of stay results
Nine of the 27 studies included in our meta-analysis mentioned LOS in MIVH versus CVH groups [14,15,18,22,27,28,30,33,36]. The results (Fig. 2) show a significant reduction of LOS in the minimally invasive group in comparison to the conventional group (random effect weighted mean difference of –1.04, CI –1.92 to –0.16).
3.10. Sensitivity analysis results
The results for sensitivity analysis using fixed and random effect models for each of the six NIWHDs are shown in Table 2. We have previously discussed the preference of random over fixed effects models in surgical statistical analyses, and will therefore mention only the former in the results below.
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When considering sensitivity analysis for all NIWHDS (Table 4), the lowest heterogeneity was identified when only randomised and only fully matched trials were included, highlighting the importance of good study design, and matching patient characteristics.
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4. Discussion |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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We have previously used meta-analysis of randomised trials comparing MIVH to CVH with regards to the incidence of post-operative leg-wound infection, which we have found to be significantly reduced in the minimally invasive group [3]. Given that this meta-analysis suggests that NIWHDs are also reduced in MIVH, it is not difficult to see how these non-infective wound complications may predispose to infection of the leg wound following harvest of the great saphenous vein. An example of this is wound dehiscence or separation, which can impair tissue healing by affecting tissue apposition, thereby predisposing to wound infection. Similarly wound haematoma may act as an infective focus following surgery. The reduction in wound-related morbidity following MIVH may have several elements, including reduced trauma to surrounding tissues, less inflammation, fewer disturbances to skin vascularisation, and finally avoidance of skin flap creation. Notably the conversion rates reported by the studies included in our analysis were variable (0–31%), highlighting the need to carefully select patients for the procedure. Evaluation of the factors that influence the need for conversion were not within the scope of this study.
The results that were calculated for NNT suggest that certain NIWHDs benefit more from MIVH than others. The lowest NNT was 2 for oedema following MIVH, which means that only 2 patients would require the intervention before benefit was seen. In contrast, haematoma, skin necrosis, dehiscence, and wound drainage all had a calculated NNT of 13. This may be because the MIVH technique involves tunnelling rather than cutting through the layers of tissue covering the vein, and therefore result in a more localised inflammatory response for wound healing. It is easy to see how the NNT for haematoma is higher as one of the advantages of CVH is that haemostasis is possible under direct vision before closing the wound. In this respect endoscopic MIVH has the added benefit over non-endoscopic MIVH in that ligation of the branches of the great saphenous vein can be done under direct vision and the wound tunnel can be inspected more easily.
Length of hospital stay results from the studies included in this meta-analysis show that MIVH significantly reduces LOS compared to CVH (Fig. 2). These results may be due to the fact that mobilisation following MIVH is improved, thereby facilitating recovery and subsequent discharge from hospital, a link that must be further researched in the future.
The limitations of our meta-analysis were as follows. First, varying definitions for the NIWHD (as illustrated in Table 2), meant that despite our efforts to standardise, our outcome measures were less well defined and therefore less absolute than we would have ideally liked. Second, neither the allocation of treatment, nor the assessment of outcome was blinded. Third, it is important to bear in mind publication bias, particularly in meta-analytic research based on published studies. Fourth, there was variation in inclusion criteria, type of randomisation used, treatment protocols, and outcome assessment between studies.
These limitations aside, we feel that we have once again illustrated an important link between minimally invasive great saphenous vein harvest and improved tissue healing when compared to conventional open surgery. A reduction in wound healing disturbances has the potential to reduce wound-related morbidity, infection, post-operative pain, length of hospital stay, and re-admission rate. This in turn has an implication not only on the cost of post-operative care that these patients receive, but their satisfaction with the operation, and therefore quality of life following surgery. It is important to note that some of the NIWHDs such as dehiscence and seroma formation are rarer than others such as oedema and thus cannot be identified using small patient groups. Trends for these healing disturbances become apparent only when a large patient group such as that in this meta-analysis, is used. Although wound infection is a significant post-operative wound complication, it is important to appreciate that a patient may suffer significant morbidity from a wound in the absence of infection. Non-infective complications appear at different (shorter) post-operative time settings in comparison to infection, and are more likely to affect LOS. Wound infection appears later and is a more prominent cause of readmission. Our study separates the effect of the two.
Finally, in addition to helping to answer the question of whether MIVH reduces NIWHD in patients undergoing cardiac surgery, this study raises several important issues regarding the factors that need to be taken into account when comparing two surgical techniques such as MIVH and CVH. This is evident in the sensitivity analysis which shows the level of heterogeneity to be lowest with studies that are randomised and of appropriate size or contain a patient group that is fully matched for age, sex, diabetes, obesity and peripheral vascular disease. These are factors that must therefore be addressed in any further research that is undertaken.
Although our study adds weight to the argument that minimally invasive great saphenous vein harvest techniques in well selected patients cause less wound-related morbidity, it important to appreciate that it does not consider other important aspects of the surgery that deserve mention. These include cost of the surgery, harvesting time required, the quality of the minimally invasively harvested conduit, and an evaluation of the different minimally invasive harvest systems (endoscopic and non-endoscopic) available. Finally there is the question of whether minimally invasively harvested veins have comparable patency rates to those harvested conventionally. It is to answer these questions that we feel further research is required.
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References |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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