Reconstructive options for complex head and neck defects that arise following resection of head and neck cancer range from microvascular free tissue transfer to loco-regional pedicled flaps. Although the former is considered the standard of care, loco-regional flaps, such as pectoralis major myocutaneous flaps, still account for the vast majority of flap procedures performed in resource-constrained high-volume oncology centres in Asia. Pedicled flaps are also relevant in the salvage setting following the failure of microvascular free tissue transfer.Reference Kanazawa, Sarukawa, Fukushima, Takeoda, Kusaka and Ichimura1

Although pedicled flaps such as pectoralis major myocutaneous flaps are robust and considered the workhorse of head and neck reconstruction even today, rates of flap necrosis range from 17 to 63 per cent.Reference Shah, Haribhakti, Loree and Sutaria2 Underlying factors responsible for the necrosis of a pedicled flap include compression of the pedicle, twisting of the pedicle, local oedema and vascular spasm.Reference Akan, Yildirim and Gideroğlu3,Reference Talbot and Pribaz4 Venous insufficiency has been found to outnumber arterial spasm following reconstruction due to either free tissue transfer or pedicled flaps.Reference Talbot and Pribaz4 The following reasons account for the greater vulnerability of venous channels: lower pressure in the venous system compared with the arterial system predisposing the former to compression injury, oedema and torsion, and insufficient venous outflow channels in some flaps, with concomitant high flow arterial influx.Reference Talbot and Pribaz4

Venous insufficiency in a pedicled flap needs to be regarded with similar weightage as in the case of free tissue transfer. Once venous insufficiency is identified, the window period available for instituting salvage measures is crucial.Reference Pérez, Sancho, Ferrer, García and Barret5 Unlike free tissue transfer, surgical re-exploration on account of venous insufficiency is not routinely undertaken for pedicled flaps.Reference Talbot and Pribaz4,Reference Pérez, Sancho, Ferrer, García and Barret5 Moreover, there are existing lacunae in the literature regarding successful salvage measures for early venous compromise in pedicled flaps. Hence, this study was undertaken to evaluate the role of low-molecular-weight heparin pedicled flaps showing signs of venous compromise.

This study prospectively evaluated the efficacy of low-molecular-weight heparin (dalteparin) in pedicled flaps used in head and neck reconstruction showing venous congestion (n = 47) compared to 26 patients who did not receive any therapeutic intervention for congestion and hence served as the control arm. In the intervention arm, 48.96 per cent of the flaps showed either reversal or non-progression of venous congestion. In the control arm (Arm B), only 1 patient showed signs of spontaneous reversal (3.8 per cent) (p = 0.002). This translated to a significant difference between the two arms in terms of incidence of complete flap necrosis at 4 weeks (Arm A 8.5 per cent, Arm B 50 per cent) (p = 0.002).

We also assessed the predictors for successful salvage and found higher salvage rates in the subset of patients where low-molecular-weight heparin was initiated in the early post-operative period (12–24 hours). The salvage rate documented in the early initiation subset was 70 per cent and the salvage rate in the subset where low-molecular-weight heparin was administered after a lapse of 24 hours was 13.3 per cent (p = 0.0015).

The options available to increase flap viability in the context of microvascular free tissue transfer are myriad. Because of the paucity of evidence for the pedicled flap, this study was designed by extrapolating the available evidence in the field of microvascular reconstruction.Reference Pérez, Sancho, Ferrer, García and Barret5 Although there is no uniform consensus even amongst microvascular surgeons, commonly employed agents targeting the coagulation pathway include heparin and its analogues, dextran, aspirin and statins.Reference Pršić, Kiwanuka, Caterson and Caterson6 An ideal antithrombotic agent in the setting of reconstruction should prolong flap viability and at the same time not cause unnecessary complications related to bleeding.Reference Chien, Varvares, Hadlock, Cheney and Deschler7 Because of the risk of post-operative haemorrhage, unfractionated heparin has been gradually replaced with low-molecular-weight heparin.Reference Numajiri, Sowa, Nishino, Arai, Tsujikawa and Ikebuchi8

Other reasons for favouring low-molecular-weight heparin over unfractionated heparin are the requirement for activated partial thromboplastin time (APTT) in the case of unfractionated heparin and the possibility of heparin-induced thrombocytopenia.Reference Pršić, Kiwanuka, Caterson and Caterson6 Unlike heparin and its analogues, which target the coagulation pathway involved in venous thrombosis, aspirin, which is a cyclooxygenase inhibitor, functions by inhibiting platelet aggregation.Reference Pršić, Kiwanuka, Caterson and Caterson6 Studies performed by Khouri et al. on the fibrin and platelet content of anastomotic clots showed higher fibrin content than platelet content, thereby recommending heparin as the primary antithrombotic agent.Reference Khouri, Cooley, Kenna and Edstrom9 However, later studies utilising scanning electron microscopy have shown equal contents of fibrin and aspirin.Reference Savoie, Cooley and Gould10 Thus, many microvascular surgeons have incorporated aspirin along with low molecular heparin in their antithrombotic armamentarium.Reference Chien, Varvares, Hadlock, Cheney and Deschler7 Nevertheless, the possible detrimental effects of combining two antithrombotic agents, as observed by Bahl et al. in their analysis involving a large database of otolaryngology patients receiving chemoprophylaxis for venous thromboembolism, should be noted.Reference Bahl, Shuman, Hu, Jackson, Pannucci and Alaniz11

The role of statins is yet to be confirmed by larger studies.Reference Pršić, Kiwanuka, Caterson and Caterson6 Dextrans have also not been used in a widespread manner owing to possible side effects relating to volume overload, compromising the cardiovascular system in susceptible individuals and anaphylactic reactions.Reference Pršić, Kiwanuka, Caterson and Caterson6

Our extensive literature search did not reveal studies performed on subcutaneous low-molecular-weight heparin salvage of compromised pedicled flaps. Thus, to the best of our knowledge, this is the only prospective study investigating the role of subcutaneous low-molecular-weight heparin in pedicled flap venous congestion. We did, however, identify one series of 9 compromised pedicled flaps where local injection of heparin showed a dramatic response, resulting in 100 per cent salvage rates.Reference Pérez, Sancho, Ferrer, García and Barret5

Unlike pedicled flaps, antithrombotic measures are routinely employed in microvascular free tissue transfer. However, the literature is conflicted over the efficacy of routine antithrombotic agent use in free flap surgery. In a meta-analysis conducted by Pan et al., no statistically significant difference in terms of flap viability was noted amongst patients receiving either heparin or aspirin.Reference Pan, Chen, Shao, Han, Zhang and Zhi12 This study also found a higher rate of flap loss in the patient group receiving high-dose low-molecular-weight heparin. The only study skewing the results against high-dose low molecular weight heparin is that by Blackburn et al., which reported higher flap loss with increasing dose of heparin, but without an increase in the incidence of bleeding-related complications.Reference Blackburn, Java, Lowe, Brown and Rogers13

In the study by Numajiri et al. on unfractionated heparin, the heparin group was shown to cause significant prolongation of APTT and prothrombin time, causing an increase in bleeding-related complications while not resulting in a significant alteration in final flap viability.Reference Numajiri, Sowa, Nishino, Arai, Tsujikawa and Ikebuchi8 Contrary to these studies, Eley et al. showed that high-dose dalteparin as used in our study did not increase bleeding risk.Reference Numajiri, Sowa, Nishino, Arai, Tsujikawa and Ikebuchi8,Reference Pan, Chen, Shao, Han, Zhang and Zhi12,Reference Blackburn, Java, Lowe, Brown and Rogers13,Reference Eley, Parker and Watt-Smith14 In addition, it was found that lower doses of dalteparin caused an insufficient level of anti-factor Xa, which is a surrogate marker for low-molecular-weight heparin efficacy.Reference Eley, Parker and Watt-Smith14

The best evidence favouring subcutaneous heparin use following free flap surgery was reported by Khouri et al.Reference Khouri, Cooley, Kunselman, Landis, Yeramian and Ingram15 In their series of 493 free flaps, subcutaneous heparin use significantly reduced thrombotic complications in the flaps. Despite the literature being conflicted, real-world data, as revealed by a survey by Glicksman et al., showed that 96 per cent of reconstructive surgeons use some form of antithrombotic measure.Reference Glicksman, Ferder, Casale, Posner, Kim and Strauch16

There is little data regarding routine antithrombotic drug administration in otorhinolaryngology outside of a free flap reconstruction.Reference Bahl, Shuman, Hu, Jackson, Pannucci and Alaniz11 The Caprini risk assessment tool is commonly used to predict the predisposition of a patient for post-operative venous thromboembolism.Reference Caprini17 In the study by Bahl et al., 30 per cent of patients with head and neck cancer and those undergoing reconstruction were found to have a Caprini score of 7 and higher compared to 16 per cent of non-oncology otolaryngology patients.Reference Bahl, Shuman, Hu, Jackson, Pannucci and Alaniz11 Although this study found subcutaneous low-molecular-weight heparin to be useful in the context of prevention of venous thromboembolism events in the above subset, results related to flap viability were not presented.

The study by Bahl et al. documented higher bleeding rates in patients receiving a combination of antiplatelet and low-molecular-weight heparin.Reference Bahl, Shuman, Hu, Jackson, Pannucci and Alaniz11 An 11.9 per cent incidence of bleeding complications was identified in patients post free flap reconstruction receiving thromboprophylaxis, which compares well with the 12.76 per cent incidence in our study.Reference Bahl, Shuman, Hu, Jackson, Pannucci and Alaniz11

Kroll et al. performed a non-randomised prospective study on 517 free flap procedures, comparing no anticoagulation, low-dose heparin bolus and post-operative infusion, high-dose intra-operative bolus and dextran.Reference Kroll, Miller, Reece, Baldwin, Robb and Bengtson18 Hematoma rates were highest in the high-dose heparin group (20 per cent) and were 6.5 per cent in the low-dose group. However, flap survival and rates of pedicle thrombosis were lower than in patients who did not receive any form of anticoagulation (p > 0.05). Similar results were also observed in the study by Khouri et al., in which hematoma rates were higher in the anticoagulation group and better results in terms of flap viability were also observed in these patients.Reference Khouri, Cooley, Kunselman, Landis, Yeramian and Ingram15

As observed in our study, although hematoma rates were high compared with the rest of the cohort, we did not record the prolongation of hospital stay, delay in initiation of feeds or adjuvant treatment owing specifically to this complication. However, the sequelae associated with a compromised flap that goes on necrose to a significant extent can be disastrous in terms of treatment package time, quality of life and requirement of a second salvage flap.

Once venous congestion sets in, time to intervention is paramount. As noted in our study (Table 3), when the time to initiation exceeded 24 hours, only 2 flaps could be satisfactorily salvaged. Our results in pedicled flaps closely correspond to the findings observed in microvascular free tissue transfer.Reference Pršić, Kiwanuka, Caterson and Caterson6 In free flaps, 90 per cent of arterial thrombi and 42 per cent of venous thrombi occurred on the first post-operative day and 95 per cent of free flap re-explorations occurred in the first 72 hours.Reference Pršić, Kiwanuka, Caterson and Caterson6

Although this study presents a novel idea to salvage pedicled flaps with early-onset venous congestion and results have been compared with a well-balanced control group, it was limited by the small sample size, especially of the control arm. The study also lacks a detailed analysis of surgical complications and other parameters of bleeding tendencies, such as the requirement for blood transfusion and the duration of surgical drain placement.

• It was found that 48.9 per cent of flaps could be effectively salvaged following the administration of low-molecular-weight heparin

• The low-molecular-weight heparin group had a significantly lower incidence of partial and complete flap loss compared with the control group

• Administration of low-molecular-weight heparin within 12–24 hours of flap congestion was associated with a higher salvage rate (odds ratio 16.6)

• The use of low-molecular-weight heparin was associated with a higher incidence of secondary haemorrhage rates