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Predicting risk factors that lead to free flap failure and vascular compromise: A single unit experience with 565 free tissue transfers

Open AccessPublished:September 19, 2020DOI:https://doi.org/10.1016/j.bjps.2020.08.126

      Summary

      Background

      Even though the benefit of free tissue transfer is uncontested in complex reconstructive cases, vascular compromise and/or flap failure remain a challenge for the surgeon and identification of possible risk factors can aid in the preoperative planning. The aim of this study was to identify the individual risk factors leading to flap failure and/or vascular compromise in free tissue transfers in a single institution over a period of 10 years and to create an index predicting these problems, as well as finding predictors of other postoperative complications.

      Methods

      Data from all the patients undergoing free tissue transfers between 2009 and 2018 were retrospectively analyzed (demographics, comorbidities, flap failure, vascular compromise, and other complications). The results from the univariate and multivariate analyses were used to create an index.

      Results

      A predictability index with three classes (low, moderate, and high risk) was calculated for each patient, based on defect etiology and the presence of coronary heart disease, diabetes, smoking, peripheral arterial vascular disease, and arterial hypertension. A patient with moderate-risk index had 9.3 times higher chances of developing vascular compromise than those in the low-risk group, while a high-risk index had 18.6 higher odds (p=0.001). American Society of Anesthesiologists (ASA) classification was found to be a predictor of complications in free tissue transfer (p=0.001).

      Conclusion

      If patients at a high risk of vascular compromise could be identified preoperatively through this predictability index, patient counseling could be improved and the surgeon might adapt the reconstructive plan and choose an alternative reconstructive strategy.

      Keywords

      Introduction

      Since 1972, when McLean and Buncke reported the first free tissue transfer, a multitude of free flaps have been envisioned and described.
      • McLean DH
      • Buncke Jr., HJ
      Autotransplant of omentum to a large scalp defect, with microsurgical revascularization.
      Free flaps are normally reserved for the most complex reconstructions and are often the only option left to the reconstructive surgeon.
      • Cannady SB
      • Rosenthal EL
      • Knott PD
      • Fritz M
      • Wax MK
      Free tissue transfer for head and neck reconstruction: a contemporary review.
      Therefore, a better understanding of the risk factors associated with flap failure and return to theater with vascular compromise requiring anastomotic revision could potentially aid the surgeons to tailor their decision-making process and provide patients with improved counseling before consenting to such complex procedures. It could also potentially lead to a different surgical strategy taking into consideration individual patient´s surgical and medical history.
      Even though great effort has been made in refining the microsurgical techniques and reducing the operator-dependent technical errors, the postoperative complications are still high.
      • Classen DA
      • Ward H.
      Complications in a consecutive series of 250 free flap operations.
      ,
      • Wettstein R
      • Schurch R
      • Banic A
      • Erni D
      • Harder Y
      Review of 197 consecutive free flap reconstructions in the lower extremity.
      Nevertheless, patients’ characteristics also seem to play an important role in the outcomes of free flaps.
      • Rao S
      • Stolle EC
      • Sher S
      • Lin CW
      • Momen B
      • Nahabedian MY
      A multiple logistic regression analysis of complications following microsurgical breast reconstruction.
      • Miller RB
      • Reece G
      • Kroll SS
      • et al.
      Microvascular breast reconstruction in the diabetic patient.
      • Serletti JM
      • Higgins JP
      • Moran S
      • Orlando GS
      Factors affecting outcome in free-tissue transfer in the elderly.
      Usually, reports are based on specific anatomical areas, for example, head and neck,
      • Hwang K
      • Lee JP
      • Yoo SY
      • Kim H
      Relationships of comorbidities and old age with postoperative complications of head and neck free flaps: a review.
      ,
      • Zhang C
      • Sun J
      • Zhu H
      • et al.
      Microsurgical free flap reconstructions of the head and neck region: Shanghai experience of 34 years and 4640 flaps.
      lower extremity
      • Xiong L
      • Gazyakan E
      • Kremer T
      • et al.
      Free flaps for reconstruction of soft tissue defects in lower extremity: a meta-analysis on microsurgical outcome and safety.
      ,
      • Reece EM
      • Bonelli MA
      • Livingston T
      • et al.
      Factors in free fasciocutaneous flap complications: a logistic regression analysis.
      or breast reconstruction.
      • O'Neill AC
      • Haykal S
      • Bagher S
      • Zhong T
      • Hofer S
      Predictors and consequences of intraoperative microvascular problems in autologous breast reconstruction.
      Therefore, it is not clear whether these previously identified risk factors for different regions have the same effect across the entire microsurgical reconstructive spectrum.
      The primary aim of this study is to identify the individual risk factors leading to flap failure and re-exploration of the microsurgical anastomosis in free tissue transfers in a single institution over a period of 10 years and to create an index predicting these problems. Secondly, the study also examines predictors of other postoperative complications.

      Patients and methods

      All patients undergoing free tissue transfer between 2009 and 2018 in the Department of Plastic and Reconstructive surgery, University Hospital in Bern, Switzerland, were considered for this study. The following patient-related data were retrospectively collected for each patient: age at time of surgery, gender, American Society of Anesthesiologists (ASA) classification, alcohol and tobacco consumption, obesity, medical comorbidities (high blood pressure, diabetes mellitus, heart failure, coronary artery disease, and others), defect etiology, defect location, and flap used. Each free flap performed was considered as a single encounter; thus, patients who received multiple free flaps at once were considered as multiple encounters, as well as free flaps performed on the same patient but at different time points.
      Flap failures, as well as vascular compromise necessitating return to theater, and all complications were recorded. In order to create an index predicting flap failure and/or vascular compromise, we analyzed surgical etiology, as well as comorbidities using the Mann-Whitney U test for the continuous variables, while Pearson's χ2 test and Fischer's exact test were conducted for the categorical variables. Depending on the results, the presence of various conditions was scored in order to create an index with low, moderate and high risk for vascular compromise, return to theater, and flap failure.
      The postoperative surgical complications (infection, partial flap necrosis, postoperative bleeding, hematoma, seroma, dehiscence, and others) were divided into minor and major complications as follows: minor complications were considered conditions that were treated conservatively, without returning to the operating theater, while major complications were the ones that required surgical reintervention. In order to analyze the complications, factors with a significance of p < 0.2 in the univariate analysis were included in the multivariate binominal logistic regression model to identify independent risk factors for postoperative complications. Statistical analysis was performed using SPSS 23.0 (SPSS Inc., Chicago, USA).
      The study was conducted according to the Declaration of Helsinki principles and was approved by the local Research Ethics Committees (ID 2018-00312).

      Results

      From 2009 to 2018, 580 free flap procedures were identified, with 15 of them having missing data. Therefore, only 565 free flaps were included in this study. Patients’ demographic and clinical characteristics are outlined in Table 1. The distribution of defect etiology, defect location and type of flap used for reconstruction are illustrated in Figure 1, Figure 2, Figure 3, respectively.
      Table 1Patients’ demographic and clinical characteristics.
      CharacteristicsCategoryNumber (%) or Median [Range]
      Patient's age52.83 [6–93]
      Gender
      Women217 (38.4%)
      Men348 (61.6%)
      ASA
      1141 (25)
      2275 (48.7)
      3139 (24.6)
      410 (1.8)
      Alcohol
      No460 (81.4)
      Yes105 (18.6)
      Smoking
      No382 (67.6)
      Yes183 (32.4)
      Obesity
      No481 (85.1)
      Yes84 (14.9)
      High Blood Pressure
      No415 (73.5)
      Yes150 (26.5)
      Diabetes mellitus
      No515 (91.2)
      Yes50 (8.8)
      Heart Failure
      No541 (95.8)
      Yes24 (4.2)
      Coronary Heart Disease
      No524 (92.7)
      Yes41 (7.3)
      Cerebrovascular Accident
      No561 (99.3)
      Yes4 (0.7)
      Peripheral Arterial Occlusive Disease
      No535 (94.7)
      Yes30 (5.3)
      COPD or Asthma
      No512 (90.6)
      Yes53 (9.4)
      Chronic venous insufficiency
      No556 (98.4)
      Yes9 (1.6)
      Comorbidity
      No283 (50.1)
      Yes282 (49.9)
      Figure 1
      Figure 1Defect etiology: 1. Elective: free tissue transfer for various cancers that were reconstructed in a delayed fashion more than three months after the initial resection, chronic osteomyelitis with plate infection or other posttraumatic complications ensuing more than 3 months after the initial surgical intervention and osteoradionecrosis; 2. Cancer: patients with various malignancies undergoing free tissue transfer immediately or at a maximum of 3 months after tumor resection; 3. Trauma: patients with soft-tissue trauma and fractures, including infections, undergoing reconstructive surgery immediately or at a maximum of 3 months after the incident.
      Figure 3
      Figure 3Flap type. *Other flap types include vertical rectus abdominis muscle flap (VRAM), medial plantar artery flap (MPAF), supraclavicular artery perforator flap (SAPF), tensor fascia lata flap (TFL), vastus lateralis muscle flap, rectus femoris muscle flap, groin flap, and serratus flap.

       Flap failures and return to theater

      There were 35 patients with vascular compromise, 14 arterial and 21 venous. In the arterial group, 10 flaps were taken back on the first postoperative day, but only 1 was saved. Both of the flaps with arterial occlusion on the second postoperative day, one flap on the third postoperative day and one flap on the forth postoperative day were lost despite revision. Therefore, we recorded a 7.1 % salvage rate among the flaps with arterial occlusion (1 out of 14). Vein occlusion occurred in 21 flaps and had a salvage rate of 85.71 % (18 out of 21). Seventeen flaps were revised on the first postoperative day, with success in 15 cases, while the other four were taken back to theater on the second postoperative day, with three of them being saved. When looking exactly at the etiology of vascular compromise that preceded flap failure, the 13 cases due to arterial occlusion proved to be statistically significant (<0.001) when compared to the venous occlusion. In the patients with arterial and venous occlusion, there was no statistically significant difference in terms of comorbidities, gender, or age.
      Table 2 summarizes the characteristics of the patients with and without vascular compromise. In order to create an index predicting flap failure and/or vascular compromise, each of the following comorbidities were assigned a score of 1: smoking, the presence of arterial hypertension, diabetes mellitus, coronary heart disease, and peripheral arterial vascular disease. We analyzed the different etiological groups and found a trend in flap failure and/or vascular compromise between the various etiologies (p<0.2): in the elective group, there were 3.8% cases with vascular compromise, while the cancer group recorded 6.9% and the trauma group had a vascular compromise rate of 8.9%. A statistical significance was reached when the elective group was compared to the trauma group (p=0.038). Based on this analysis, we assigned the following predictability score to each etiological group: elective – 1, cancer – 2 and trauma – 3. This allowed us to create a predictability index ranging from 1 to 8 points calculated for each patient. In order to predict the risk of vascular compromise, we subdivided the predictability index in three groups: low risk (index 1 and 2), moderate risk (index 3, 4, and 5), and high risk (index 6, 7, and 8). Table 3 shows the vascular compromise rate in each group. In the binominal logistic regression analysis, increasing index group was associated with an increased likelihood of exhibiting vascular compromise (p=0.001): a patient with a moderate-risk index had 9.3 times higher chances of developing vascular compromise than those in the low-risk group, while a high-risk index had 18.6 higher odds. Therefore, our predictability index appeared to be an accurate predictor of flap failure and/or vascular compromise. However, it is not able to predict flap salvage. These findings were supported to a certain extent by the ASA score, but only when comparing ASA 4 to ASA 1, since the other scores did not reach statistical significance: a patient with ASA 4 has a 9.6 times higher chance of having problems with flap failure and/or vascular compromise than a patient with ASA 1.
      Table 2Univariate risk factor analysis for flap failure and/or vascular compromise.
      CharacteristicNo Flap Failure and/or Vascular CompromiseFlap Failure and/or Vascular CompromiseP value
      Patient's age51.24 6-9350.13 17-780.715
      Gender0.381
      Female206 (94.9)11 (5.1)
      Male324 (93.1)24 (6.9)
      ASA score0.012
      ASA 1135 (95.7)6 (4.3)
      ASA 2259 (94.2)16 (5.8)
      ASA 3129 (92.8)10 (7.2)
      ASA 47 (70)3 (30)
      Alcohol0.947
      No431 (93.7)29 (6.3)
      Yes99 (94.28)6 (5.72)
      Smoking0.004
      No366 (95.8)16 (4.2)
      Yes164 (89.6)19 (10.4)
      Obesity0.378
      No453 (94.2(28 (5.8)
      Yes77 (91.7)7 (8.3)
      Arterial Hypertension0.063
      No394 (94.9)21 (5.1)
      Yes136 (90.7)14 (9.3)
      Diabetes mellitus0.000
      No494 (95.9)21 (4.1)
      Yes36 (72)14 (28)
      Heart failure0.657
      No508 (93.9)33 (6.1)
      Yes22 (91.7)2 (8.3)
      Cerebrovascular accident0.606
      No526 (93.8)35 (6.2)
      Yes4 (100)0 (0)
      Coronary heart disease0.000
      No501 (95.6)23 (4.4)
      Yes29 (70.7)12 (29.3)
      Peripheral arterial vascular disease0.000
      No509 (95.1)26 (4.9)
      Yes21 (70)9 (30)
      COPD or Asthma0.304
      No482 (94.1)30 (5.9)
      Yes48 (90.6)5 (9.4)
      Chronic venous insufficiency0.437
      No521 (93.7)35(6.3)
      Yes9 (100)0 (0)
      Defect etiology0.115
      Elective225 (96.2)9 (3.8)
      Cancer161 (93.1)12 (6.9)
      Trauma144 (91.1)14 (8.9)
      Defect Location0.329
      Head & Neck178 (93.7)12 (6.3)
      Trunk12 (100)0 (0)
      Breast71 (98.6)1 (1.4)
      Upper Extremity34 (91.9)3 (8.1)
      Lower Extremity235 (92.5)19 (7.5)
      Flap type0.555
      ALT171 (93.4)12 (6.6)
      Gracilis74 (93.7)5 (6.3)
      Latissimus dorsi72 (92.3)6 (7.7)
      Fibula70 (93.3)5 (6.7)
      Scap/Parascap45 (95.7)2 (4.3)
      DIEP39 (97.5)1 (2.5)
      TRAM32 (100)0 (0)
      Radialis11 (91.7)1 (8.3)
      Other16 (84.2)3 (15.8)
      Table 3Flap failure and/or vascular compromise predictability index.
      Predictability IndexNo Flap Failure and/or Vascular CompromiseFlap Failure and/or Vascular Compromise
      Low-risk (index 1 & 2)
      Number2513
      Percentage98.8 %1.2 %
      Moderate-risk (index 3, 4 & 5)
      Number27030
      Percentage90 %10 %
      High-risk (index 6, 7 & 8)
      Number92
      Percentage81.8%18.2 %

       Postoperative complications

      An overview of the postoperative complications is presented in Table 4. There were 183 flaps (32.4 %) with other postoperative complications, with some patients experiencing only minor or major complications, while others were treated both conservatively and surgically for the postoperative complications. In total, there were 42 minor complications (7.4 %) and 152 major complications (26.9 %).
      Table 4Other postoperative complications.
      ComplicationNumber (% from total flaps)Minor (% from total flaps)Major (% from total flaps)
      Infection56 (9.9)5 (0.9)51 (9)
      Partial Flap Necrosis89 (15.8)10 (1.8)79 (14)
      Postoperative bleeding13 (2.3)1 (0.2)12 (2.1)
      Hematoma52 (9.2)9 (1.6)43 (7.6)
      Seroma6 (1.1)3 (0.5)3 (0.5)
      Wound dehiscence46 (8.1)11 (1.9)35 (6.2)
      Other complication7 (1.2)7 (1.2)0
      * Other complications include fistula, wound healing disorder, and tissue volume excess.
      The results of the univariate and multivariate analysis are summarized in Tables 5 and 6, respectively. The ASA score, along with the presence of diabetes and cerebrovascular accident, showed statistical significance (p<0.05). Since the ASA score was overlapping with the various comorbidities, we decided to use the ASA score as the sole comorbidity representative in the logistic regression, as well as the other variables with p<0.2. Of all the predictors, only two were statistically significant: the ASA score and flap type. Patients with ASA 2 had 2.2 times higher odds to develop postoperative complications, while ASA 3 increased the chances by 2.6. Patients with ASA 4 had 11.8 times increased chances of postoperative complications in comparison to patients with ASA 1. Moreover, the flap type also had an influence on postoperative complications: patients undergoing free osteo-septo-cutaneous fibula flap recorded a 2.33 times higher chance of developing postoperative complications.
      Table 5Univariate risk factor analysis for other postoperative complications.
      CharacteristicNo ComplicationsComplicationsP value
      Patient's age50.47 [9–93]52.72 [6–87]0.257
      Gender0.087
      Female144 (69.9)62 (30.1)
      Male203 (62.7)121 (37.3)
      ASA score0.001
      ASA 1105 (77.8)30 (22.2)
      ASA 2164 (63.3)95 (36.7)
      ASA 376 (58.9)53 (41.1)
      ASA 42 (28.6)5 (71.4)
      Alcohol0.335
      No285 (66.1)146 (33.9)
      Yes62 (62.6)37 (37.4)
      Smoking0.288
      No245 (66.9)121 (33.1)
      Yes102 (62.2)62 (37.8)
      Obesity0.160
      No302 (66.7)151 (33.3)
      Yes45 (58.4)32 (41.6)
      Arterial Hypertension0.398
      No262 (66.5)132 (33.5)
      Yes85 (62.5)51 (37.5)
      Diabetes mellitus0.043
      No329 (66.6)165 (33.4)
      Yes18 (50)18 (50)
      Heart failure0.785
      No332 (65.4)176 (34.6)
      Yes15 (68.2)7 (31.8)
      Cerebrovascular accident0.006
      No347 (66)179 (34)
      Yes0 (0)4 (100)
      Coronary heart disease0.692
      No329 (65.7)172 (34.3)
      Yes18 (62.1)11 (37.9)
      Peripheral arterial vascular disease0.198
      No336 (66)173 (34)
      Yes11 (52.4)10 (47.6)
      COPD or Asthma0.440
      No318 (66)164 (34)
      Yes29 (60.4)19 (39.6)
      Chronic venous insufficiency.939
      No341 (65.5)180 (34.5)
      Yes6 (66.7)3 (33.3)
      Defect etiology0.664
      Elective151 (67.1)74 (32.9)
      Cancer101 (62.7)60 (37.3)
      Trauma95 (66)49 (34)
      Defect Location0.397
      Head & Neck115 (64.6)63 (35.4)
      Trunk7 (58.3)5 (41.7)
      Breast51 (71.8)20 (28.2)
      Upper Extremity26 (76.5)18 (23.5)
      Lower Extremity148 (63)87 (37)
      Flap type0.063
      ALT115 (67.3)56 (32.7)
      Gracilis55 (74.3)19 (25.7)
      Latissimus dorsi45 (62.5)27 (37.5)
      Fibula35 (50)35 (50)
      Scap/Parascap28 (62.2)17 (37.8)
      DIEP24 (61.5)15 (38.5)
      TRAM26 (81.3)6 (18.7)
      Radialis8 (72.7)3 (27.3)
      Other11 (68.8)5 (31.3)
      * COPD=Chronic Obstructive Pulmonary Disease.
      Table 6Multivariate risk factor analysis for other postoperative complications.
      BEXP(B) = ORSig.95% CI for EXP(B)
      LowerUpper
      Gender−.316.729.167.4651.142
      ASA 1.001
       ASA 2.7872.197.0021.3453.589
       ASA 3.9562.601.0011.4904.542
       ASA 42.47111.829.0052.12265.956
      Flap Type (ALT).012
       Gracilis muscle flap−.330.719.304.3831.348
       Latissimus dorsi flap.1561.169.605.6472.110
       Fibula flap.8482.334.0041.3024.185
       Scapular/Parascapular flap.4331.543.229.7613.128
       DIEP flap.5731.774.168.7854.008
       TRAM flap−.480.619.358.2231.720
       Radialis flap.0981.103.891.2694.521
       Other flap.0711.074.901.3483.319
      Constant−1.356.258.084

      Discussion

       Flap failures and return to theater

      The advances achieved in microsurgery have given surgeons the armamentarium to deal with some of the most complex defects. Free tissue transfer has achieved widespread popularity and can be considered a safe and reliable method, yielding success rates between 92.3% and 98%.
      • Zhang C
      • Sun J
      • Zhu H
      • et al.
      Microsurgical free flap reconstructions of the head and neck region: Shanghai experience of 34 years and 4640 flaps.
      ,
      • Xiong L
      • Gazyakan E
      • Kremer T
      • et al.
      Free flaps for reconstruction of soft tissue defects in lower extremity: a meta-analysis on microsurgical outcome and safety.
      ,
      • Citron I
      • Galiwango G
      • Hodges A
      Challenges in global microsurgery: a six year review of outcomes at an East African hospital.
      • Chang EI
      • Nguyen AT
      • Hughes JK
      • et al.
      Optimization of free-flap limb salvage and maximizing function and quality of life following oncologic resection: 12-year experience.
      • Kwok AC
      • Agarwal JP.
      An analysis of free flap failure using the ACS NSQIP database. Does flap site and flap type matter?.
      Even though the benefit of free flap reconstruction is uncontested in successful cases, vascular compromise and/or flap failure still remain a challenge for the surgeon, and identification of possible risk factors can aid in the preoperative planning and counseling of the patient. Our index allows the reconstructive surgeon to stratify the risk for vascular compromise and in certain situations, it may aid in adjusting the reconstructive plan. Even though our flap success rate was well within the range of acceptability of reported series (97.2%), we aimed to identify the factors playing a significant role in flap failure and/or vascular compromise in our hands and if possible, produce an index predicting these problems in practice and hopefully then be able to adjust or modify our reconstructive plan in the future.
      Most series in the literature looking at flap failure and risk factors is restricted to a specific practice, for example, head and neck or breast reconstruction, while our series deals with the entire spectrum of reconstructive surgery. On the one hand, studies
      • Yoshimoto S
      • Kawabata K
      • Mitani H
      Factors involved in free flap thrombosis after reconstructive surgery for head and neck cancer.
      ,
      • Mucke T
      • Rau A
      • Weitz J
      • et al.
      Influence of irradiation and oncologic surgery on head and neck microsurgical reconstructions.
      looking at head and neck cases found that smoking, diabetes, heart disease and the presence of comorbidities were not risk factors for flap thrombosis in their univariate analysis. The lack of these variables as risk factors was also reported in a breast reconstruction study,
      • O'Neill AC
      • Haykal S
      • Bagher S
      • Zhong T
      • Hofer S
      Predictors and consequences of intraoperative microvascular problems in autologous breast reconstruction.
      although smoking was near the statistical significance limit. On the other hand, in our series covering the entire reconstructive field, the presence of arterial hypertension, diabetes, coronary heart disease, peripheral arterial occlusive disease and smoking, in combination with the etiology of the surgery constructed as an index, was highly associated with flap failure and/or vascular compromise. The vessel architecture and tissue perfusion changes induced by diabetes and therefore the increased risk for flap failure were reported by various authors.
      • Rosado P
      • Cheng HT
      • Wu CM
      • Wei FC
      Influence of diabetes mellitus on postoperative complications and failure in head and neck free flap reconstruction: a systematic review and meta-analysis.
      ,
      • Ishimaru M
      • Ono S
      • Suzuki S
      • Matsui H
      • Fushimi K
      • Yasunaga H
      Risk factors for free flap failure in 2,846 patients with head and neck cancer: a national database study in Japan.
      Moreover, the peripheral arterial occlusive disease affecting mainly the donor vessels also seems to play a significant role in flap failure.
      • Serletti JM
      • Higgins JP
      • Moran S
      • Orlando GS
      Factors affecting outcome in free-tissue transfer in the elderly.
      ,
      • Ishimaru M
      • Ono S
      • Suzuki S
      • Matsui H
      • Fushimi K
      • Yasunaga H
      Risk factors for free flap failure in 2,846 patients with head and neck cancer: a national database study in Japan.
      The endothelial dysfunction caused by smoking might explain its relation with increased vascular compromise as a contributing factor to our predictability index, but we could not reach the same statistical significance when differentiating between arterial and venous occlusion, as O'Neill et al.
      • O'Neill AC
      • Haykal S
      • Bagher S
      • Zhong T
      • Hofer S
      Predictors and consequences of intraoperative microvascular problems in autologous breast reconstruction.
      did in their study.
      Even though the ASA score was used to assess the perioperative risk of patients undergoing surgery, the extreme ASA 4 also seemed to be related with the odds of developing vascular compromise, therefore acting as a different marker for validating our index. Mücke et al.
      • Mucke T
      • Rau A
      • Weitz J
      • et al.
      Influence of irradiation and oncologic surgery on head and neck microsurgical reconstructions.
      also stated the presence of a significant inverse correlation between the ASA score and free flap survival, but its simplicity was considered a major drawback and does not include etiological factors like the index.
      The low flap salvage rate in the patients with arterial thrombosis was also observed in other studies. Nakatsuka et al.
      • Nakatsuka T
      • Harii K
      • Asato H
      • et al.
      Analytic review of 2372 free flap transfers for head and neck reconstruction following cancer resection.
      recorded 85% failure rate in the arterial thrombosis group and only 40% failure rate in the venous thrombosis group, and Chiu et al.
      • Chiu YH
      • Chang DH
      • Perng CK
      Vascular Complications and free flap salvage in head and neck reconstructive surgery: analysis of 150 cases of reexploration.
      obtained statistically significant values when looking at flap salvage among arterial and venous thrombosis, with a venous thrombosis salvage rate of 68.8%. This can be explained by the easier detection of venous congestion and also by the compensatory oozing through the flap margins and therefore delay of the irreversible damage on the flap. In their head and neck series, they report a thrombosis rate of 4%, while their lower extremity rate was around 19.7%. In our series, 6.2% of the patients recorded vascular compromise, but we could not find any statistically significant difference when looking at defect location. Even though the increased rate of atherosclerosis and vascular damage found among patients with advanced age might suggest an increased thrombosis rate, our study, as well as other authors, does not support this belief,
      • Mucke T
      • Rau A
      • Weitz J
      • et al.
      Influence of irradiation and oncologic surgery on head and neck microsurgical reconstructions.
      ,
      • Wester JL
      • Lindau RH
      • Wax MK
      Efficacy of free flap reconstruction of the head and neck in patients 90 years and older.
      making free tissue transfer in elderly a safe and reliable procedure. Arterial thrombosis usually occurs on the first postoperative day.
      • Kroll SS
      • Schusterman MA
      • Reece GP
      • et al.
      Timing of pedicle thrombosis and flap loss after free-tissue transfer.
      Our results support this finding and also reinforce the fact that arterial thrombosis has a lower salvage rate, with only one flap saved out of the 14 with arterial thrombosis. This difference between arterial and venous occlusion has also been postulated by others,
      • Yoshimoto S
      • Kawabata K
      • Mitani H
      Factors involved in free flap thrombosis after reconstructive surgery for head and neck cancer.
      ,
      • Selber JC
      • Angel Soto-Miranda M
      • Liu J
      • Robb G
      The survival curve: factors impacting the outcome of free flap take-backs.
      with the conclusion that a thrombus will damage the arterial intima, while the vein seems to be more resilient. Overall, our flap salvage rate among the flaps with vascular compromise (54.3%) is close to the one of 59.7% reported by Chiu et al.
      In the progression of the index groups, the stepwise increase in the proportion of vascular compromise could be useful in the daily decision-making process when dealing with patients undergoing such complex procedures. The 18.6 times increased incidence of a high-risk patient when compared to a low-risk one to develop vascular compromise and/or flap failure should prompt the surgeon to reassess the indication and may be adopt an alternative surgical strategy.

       Postoperative complications

      Our minor (7.4%), major (26.9%) and overall surgical complications (32.4 %) situated themselves among the values reported in the literature, as shown in Table 7.
      • Classen DA
      • Ward H.
      Complications in a consecutive series of 250 free flap operations.
      ,4,
      • Chang EI
      • Vaca L
      • DaLio AL
      • Festekjian JH
      • Crisera CA
      Assessment of advanced age as a risk factor in microvascular breast reconstruction.
      • Cornejo A
      • Ivatury S
      • Crane CN
      • Myers JG
      • Wang HT
      Analysis of free flap complications and utilization of intensive care unit monitoring.
      • Handschel J
      • Burghardt S
      • Naujoks C
      • Kubler NR
      • Giers G
      Parameters predicting complications in flap surgery.
      • Pohlenz P
      • Klatt J
      • Schon G
      • Blessmann M
      • Li L
      • Schmelzle R
      Microvascular free flaps in head and neck surgery: complications and outcome of 1000 flaps.
      • Wink JD
      • Nelson JA
      • Fischer JP
      • Cleveland EC
      • Kovach 3rd, SJ
      Free tissue transfer for complex reconstruction of the lower extremity: experience of a young microsurgeon.
      • Wu CC
      • Lin PY
      • Chew KY
      • Kuo YR
      Free tissue transfers in head and neck reconstruction: complications, outcomes and strategies for management of flap failure: analysis of 2019 flaps in single institute.
      It is of course difficult to adequately assess the scope of postoperative complications ranging from donor site complications with a minimal impact on reconstructive outcome to recipient site complication leading in the worst case scenario to flap or reconstructive failure. Nonetheless, the presence of a postoperative complication leading to surgical reintervention definitely has a decisive impact on extremely relevant issues like treatment-associated morbidity and cost.
      Table 7Complication rates in the literature.
      ArticleMinor complications (%)Major complications (%)Overall surgical complications (%)
      Classen et al.
      • Classen DA
      • Ward H.
      Complications in a consecutive series of 250 free flap operations.
      2019.239.2
      Wu et al.
      • Wu CC
      • Lin PY
      • Chew KY
      • Kuo YR
      Free tissue transfers in head and neck reconstruction: complications, outcomes and strategies for management of flap failure: analysis of 2019 flaps in single institute.
      9.9
      Wink et al.
      • Wink JD
      • Nelson JA
      • Fischer JP
      • Cleveland EC
      • Kovach 3rd, SJ
      Free tissue transfer for complex reconstruction of the lower extremity: experience of a young microsurgeon.
      1813.129.5
      Handschel et al.
      • Handschel J
      • Burghardt S
      • Naujoks C
      • Kubler NR
      • Giers G
      Parameters predicting complications in flap surgery.
      23
      Cornejo et al.
      • Cornejo A
      • Ivatury S
      • Crane CN
      • Myers JG
      • Wang HT
      Analysis of free flap complications and utilization of intensive care unit monitoring.
      22.35
      Pohlenz et al.
      • Pohlenz P
      • Klatt J
      • Schon G
      • Blessmann M
      • Li L
      • Schmelzle R
      Microvascular free flaps in head and neck surgery: complications and outcome of 1000 flaps.
      35.722
      Chang et al.
      • Chang EI
      • Vaca L
      • DaLio AL
      • Festekjian JH
      • Crisera CA
      Assessment of advanced age as a risk factor in microvascular breast reconstruction.
      33.3
      Wettstein et al.
      • Wettstein R
      • Schurch R
      • Banic A
      • Erni D
      • Harder Y
      Review of 197 consecutive free flap reconstructions in the lower extremity.
      2840
      Even though many studies have tried to identify risk factors involved in postoperative complications,
      • Las DE
      • de Jong T
      • Zuidam JM
      • Verweij NM
      • Hovius SE
      • Mureau MA
      Identification of independent risk factors for flap failure: A retrospective analysis of 1530 free flaps for breast, head and neck and extremity reconstruction.
      • Mucke T
      • Ritschl LM
      • Roth M
      • et al.
      Predictors of free flap loss in the head and neck region: A four-year retrospective study with 451 microvascular transplants at a single centre.
      • Lo SL
      • Yen YH
      • Lee PJ
      • Liu CC
      • Pu CM
      Factors influencing postoperative complications in reconstructive microsurgery for head and neck cancer.
      there are many contradictory results, and therefore, relevant risk factors are yet to be definitively identified. The only statistically significant variables in the univariate analysis were the ASA score, the presence of diabetes mellitus and history of cerebrovascular accident. Some studies have also reported increased complications in patients with diabetes,
      • Lo SL
      • Yen YH
      • Lee PJ
      • Liu CC
      • Pu CM
      Factors influencing postoperative complications in reconstructive microsurgery for head and neck cancer.
      ,
      • Fischer JP
      • Wink JD
      • Nelson JA
      • et al.
      A retrospective review of outcomes and flap selection in free tissue transfers for complex lower extremity reconstruction.
      while others reported no correlation between the disease and the outcome.
      • Chang EI
      • Nguyen AT
      • Hughes JK
      • et al.
      Optimization of free-flap limb salvage and maximizing function and quality of life following oncologic resection: 12-year experience.
      ,
      • Mucke T
      • Ritschl LM
      • Roth M
      • et al.
      Predictors of free flap loss in the head and neck region: A four-year retrospective study with 451 microvascular transplants at a single centre.
      The presence of at least one comorbidity,
      • Hwang K
      • Lee JP
      • Yoo SY
      • Kim H
      Relationships of comorbidities and old age with postoperative complications of head and neck free flaps: a review.
      ,
      • Fischer JP
      • Wink JD
      • Nelson JA
      • et al.
      A retrospective review of outcomes and flap selection in free tissue transfers for complex lower extremity reconstruction.
      as well as the preoperative medical condition of the patient assessed through the Kaplan–Feinstein index,
      • Dassonville O
      • Poissonnet G
      • Chamorey E
      • et al.
      Head and neck reconstruction with free flaps: a report on 213 cases.
      ASA status,
      • Hwang K
      • Lee JP
      • Yoo SY
      • Kim H
      Relationships of comorbidities and old age with postoperative complications of head and neck free flaps: a review.
      or the Charlson comorbidity index,
      • Khouri RK
      • Cooley BC
      • Kunselman AR
      • et al.
      A prospective study of microvascular free-flap surgery and outcome.
      was found to influence postoperative complications.
      In contrast to other studies, where age,
      • Hwang K
      • Lee JP
      • Yoo SY
      • Kim H
      Relationships of comorbidities and old age with postoperative complications of head and neck free flaps: a review.
      smoking,
      • Rao S
      • Stolle EC
      • Sher S
      • Lin CW
      • Momen B
      • Nahabedian MY
      A multiple logistic regression analysis of complications following microsurgical breast reconstruction.
      obesity
      • Rao S
      • Stolle EC
      • Sher S
      • Lin CW
      • Momen B
      • Nahabedian MY
      A multiple logistic regression analysis of complications following microsurgical breast reconstruction.
      and gender
      • Sanati-Mehrizy P
      • Massenburg BB
      • Rozehnal JM
      • Ingargiola MJ
      • Hernandez Rosa J
      • Taub PJ
      Risk factors leading to free flap failure: analysis from the national surgical quality improvement program database.
      were reported to increase postoperative complications, our study could not identify any statistically significant differences regarding these variables between patients with and without complications. Our results coincide with some of the latest studies, where complications were not influenced by gender,
      • Mucke T
      • Ritschl LM
      • Roth M
      • et al.
      Predictors of free flap loss in the head and neck region: A four-year retrospective study with 451 microvascular transplants at a single centre.
      defect location,
      • Kwok AC
      • Agarwal JP.
      An analysis of free flap failure using the ACS NSQIP database. Does flap site and flap type matter?.
      obesity,
      • de la Garza G
      • Militsakh O
      • Panwar A
      • et al.
      Obesity and perioperative complications in head and neck free tissue reconstruction.
      smoking
      • Reece EM
      • Bonelli MA
      • Livingston T
      • et al.
      Factors in free fasciocutaneous flap complications: a logistic regression analysis.
      ,
      • Chang EI
      • Nguyen AT
      • Hughes JK
      • et al.
      Optimization of free-flap limb salvage and maximizing function and quality of life following oncologic resection: 12-year experience.
      or age.
      • Reece EM
      • Bonelli MA
      • Livingston T
      • et al.
      Factors in free fasciocutaneous flap complications: a logistic regression analysis.
      While isolated variables are unlikely to be reliable predictors for all forms of morbidity and since most of the results in the literature arise from statistical tests that do not take into account the confounding factors,
      • Handschel J
      • Burghardt S
      • Naujoks C
      • Kubler NR
      • Giers G
      Parameters predicting complications in flap surgery.
      ,
      • Lo SL
      • Yen YH
      • Lee PJ
      • Liu CC
      • Pu CM
      Factors influencing postoperative complications in reconstructive microsurgery for head and neck cancer.
      we conducted the multivariate analysis. The increased risk of suffering postoperative complications in patients undergoing free fibula transfer in comparison to the ALT flap (Odds Ratio = 2.334, [95% CI] 1.3–4.2) was also reported in other studies, where reintervention, fistula, hematoma and partial necrosis rates were statistically significantly higher in bone-containing free flaps than in pure soft-tissue transfers.
      • Mucke T
      • Rau A
      • Weitz J
      • et al.
      Influence of irradiation and oncologic surgery on head and neck microsurgical reconstructions.
      ,
      • Wu CC
      • Lin PY
      • Chew KY
      • Kuo YR
      Free tissue transfers in head and neck reconstruction: complications, outcomes and strategies for management of flap failure: analysis of 2019 flaps in single institute.
      Moreover, O'Brien et al.
      • O'Brien CJ
      • Lee KK
      • Stern HS
      • et al.
      Evaluation of 250 free-flap reconstructions after resection of tumours of the head and neck.
      and Suh et al.
      • Suh JD
      • Sercarz JA
      • Abemayor E
      • et al.
      Analysis of outcome and complications in 400 cases of microvascular head and neck reconstruction.
      found this type of flap to be associated with higher rates of flap failure.

       Limitations

      The retrospective design that can account for observer bias is a limitation of our study. Since we envisioned this predictability index, we started collecting prospectively data on free tissue transfer, but this study is still ongoing. We expect the results to further validate our index. Moreover, operative time was not considered because it included the overall operation time, including other procedures such as tumor ablation, osteosynthesis, or intraoperative radiotherapy.

      Conclusion

      Microvascular free tissue transfer for complex reconstructions has proven to be reliable and safe with a low flap failure rate, although the associated complication risk is high. The patients with postoperative vascular compromise could benefit from an index that estimates this risk. If patients at a high risk of arterial or venous occlusion could be identified preoperatively, additional safety measures could be taken or the surgeon may select an alternative reconstructive strategy. This predictability index could be used in the preoperative setting to improve patient counseling, as well as treatment algorithms.

      Declaration of Competing Interest

      None declared.

      Funding

      None.

      Ethical approval

      The study was conducted according to the Declaration of Helsinki principles and approved by the local Research Ethics Committees.

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