Abstract
Free vascularized graft or free-flap reconstruction is frequently used in the reconstruction of defects in head and neck oncology patients. A common complication in free-flap surgery is thrombosis. Thrombosis occurs in 8–14% of cases and often leads to flap failure. A review of the literature on this subject was carried out and Dutch head and neck cancer centres were asked to share their guidelines concerning the prevention of thrombosis after free vascularized graft surgery. No consensus in the literature was found on how thrombosis could best be prevented. The Dutch Head and Neck Cancer Centers use routine deep venous thrombosis prophylaxis to prevent thrombosis in the anastomosis. It was also concluded that non-pharmacologic measures for preventing thrombosis, such as meticulous microvascular surgery and smoking cessation prior to the operation, are thought to play an important role in the prevention of thrombosis in microvascular free-flap reconstructions. It has not been determined which pre- and postoperative pharmacologic measure can prevent thrombosis most effectively. A pharmacologic regimen to prevent thrombosis that is customized to the patient is suggested. This should be based on an individual risk profile for the development of thrombosis.
Free vascularized grafts are frequently used in the reconstruction of defects in head and neck oncology. These reconstructions can be used for soft tissue and bony defects . Many studies on the outcomes and complications of this reconstruction technique have been carried out . Given the high reported success rates, ranging from 91 to 99% , this technique is very reliable .
Independent of the success of this technique, complications are not uncommon because head and neck oncology patients frequently suffer from comorbidities . These conditions, such as diabetes mellitus, advanced atherosclerosis or other cardiovascular diseases influence the incidence of complications and are likely to impair the quality of the vessel wall and wound healing in general . Factors such as old age and the presence of tumour are considered to be risk factors for venous thrombolytic events . Nutritional status, previous neck dissections or radiotherapy are also believed to have a negative impact on the vessel wall. Impaired quality of the vessel wall may lead to thrombotic events. Thrombosis is a frequent complication in free-flap surgery. Thrombosis occurs in 8–14% of cases and often leads to flap failure (1–9%) . Flap failure due to thrombosis in the head and neck region is, in most cases, caused by venous and not arterial thrombosis .
There are no evidence-based guidelines for the prevention of microvascular thrombosis after free vascularized graft surgery in the head and neck. The management of these patients is generally based on individual clinical experience. This article provides a review of the literature on this subject and outlines the current policy concerning the regimens of anticoagulation and other ways to prevent microvascular thrombosis after free vascularized graft surgery in the Dutch Head and Neck Cancer Centers (DHNCCs).
Materials and methods
An extensive search was performed for English-language publications and guidelines concerning microvascular thrombosis after free vascularized graft reconstruction and its prevention in Pubmed and Embase. Search and [MeSH] terms included: [aspirin], ‘anticoagulation’, ‘free-flap’, ‘free vascularized graft’, [guidelines], ‘head and neck’, [heparin], [Low Molecular Weight Heparin (LMWH)], [microsurgery], ‘microvascular surgery’, ‘protocols’ and [thrombosis]. Two authors (MTB and SCvdB) independently searched the literature. The initial search, in which randomized clinical trials (RCT) were prioritized, retrieved three studies . In the next search, retrospective studies and animal studies were also included. Case-reports were excluded. Reports on clinical series of free-flap surgeries were included when the study contained detailed information on the pharmacologic regimen. A final selection was based on the abstracts. 12 abstracts met the criteria . The results of this search were divided into two categories: studies on pharmacologic regimens and studies on other measures to prevent microvascular thrombosis.
Finally the DHNCCs were asked to share their guidelines for the prevention of thrombosis after free-flap surgery. It was assumed that these guidelines would be diverse. To get a complete overview, only open-ended questions were asked. Each centre was asked what pharmacologic and non-pharmacologic measures were used to prevent thrombosis after a free vascularized tissue transfer in the head and neck. When necessary, the DHNCC was asked for further clarification of its guidelines. Preventive measures were divided in pharmacological and non-pharmacological measures.
Results
Pharmacologic regimens: literature
No international guidelines were found for the use of anticoagulation in microvascular free-flap reconstruction in head and neck oncology.
Three RCTs could be included. D isa et al. compared three antithrombotic prophylaxis regimens in the head and neck region: first dextran 20 cc/h for 48 h, second dextran 20 cc/h for 120 h and third aspirin 325 mg/day for 120 h. These regimens were not significantly different in the incidence of thrombosis and subsequent flap survival. The groups using dextran as prophylaxis had a significantly higher rate of systemic complications . K houri et al. compared three types of intraluminal irrigating solution . In the first group, anastomoses were irrigated with a high dose of recombinant human tissue factor inhibitor (rhTFPI), in the second group a low dose was used and the third group used regular heparin. There were no significant differences in postoperative thrombosis rate. The authors concluded that the use of rhTFPI may only reduce the occurrence of postoperative complications such as hematomas . The third trial investigated the peroperative use of milrinone, a phosphodiesterase. The use of milrinone did not improve free-flap survival and had no significant influence on the occurrence of thrombosis .
A British survey on early postoperative care for free-flap head and neck reconstruction concluded that there was no consensus on the postoperative care regimen . As far as postoperative anticoagulation was concerned, only a minority of hospitals used standard postoperative anticoagulation . A survey on the postoperative use of dextran in microsurgery also concluded that there is a considerable variation in postoperative pharmacologic regimens . Table 1 summarizes the pharmacologic regimen used in nine large clinical series of head and neck reconstructions with free vascularized grafts . Low molecular weight heparin (LMWH) and heparin are used most frequently for anticoagulation. In addition, aspirin and prostaglandin are used.
| Study | Pharmacologic regimen | n | Free-flap failure (%) | Re-exploration (%) | Thrombosis (%) |
|---|---|---|---|---|---|
| Eckhardt et al. (2003) | LMWH (Dextran 40, 24–48 h after the operation) | 500 | 6% | 8% | – |
| Nahabedian et al. (2004) | Heparin 5000 I.U. 5 min before transecting the artery and vein of the flap | 102 | 5% | 8.8% | 8.8% |
| Irrigation with heparin solution | |||||
| Dextran 40 (30 ml/h for days) | |||||
| On indication: s.c. heparin injections | |||||
| Nakamizo et al. (2004) | Prostaglandin E1, 60–120 μg/day during 5 days after the operation | 187 | 2.7% | 1.1% | 2.14% |
| Suh et al. (2004) | Perioperative irrigation of donor and recipient veins with heparinized saline solution | 400 | 0.8% | 1.8% | Unknown |
| 81 mg aspirin during 7 days after the operation | |||||
| Dassonville et al. (2007) | LMWH | 213 | 6.6% | 15% | 14.1% |
| Pohlenz et al. (2007) | Heparin 200 I.U./kg bw/24 h, during 1 week after the operation | 202 | 6.2% | 10.4% | 7.9% |
| Chernichenko et al. (2008) | 81 mg aspirin during 14 days after the operation | 124 | 2.4% | Unknown | 3.2% |
| Fukuiwa et al. (2008) | 80 μg of prostaglandin E1 (Alprostadil) for 5 days after surgery | 102 | 5.9% | Unknown | 5.9% |
| Chalian et al. (2001) | Low molecular weight dextran (LMWD) was given in continuous intravenous infusion. Postoperative: low-dose heparin or LMWD for 5 days | 156 | 1% | 3.8% | Unknown |
| A bolus of 1500 units of IV heparin immediately before releasing the vascular clamps, followed by a continuous IV infusion of heparin at 300 units/h for 5 days |
Pharmacologic regimens: DHNCCs
All eight DHNCCs were invited to share their guidelines; six centres participated. An overview is presented in Table 2 . Most centres have, apart from routine DVT prophylaxis, no special regimens to prevent thrombosis. One centre has a special protocol for DVT prophylaxis in head and neck cancer patients which consists of administration of fraxiparine twice a day instead of once a day in the regular DVT prophylaxis regimen. Only two centres use a peroperative heparinized solution to flush the vessels. The other four centres do not administer any peroperative anticoagulation during flap raising.
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | |
|---|---|---|---|---|---|---|---|---|
| Centre 1 | 30 | 3 | 298 | 95% | None | Nadroparine 0.3 mL/2850 E s.c./day | Irrigation with heparinized solution | Nadroparine 0.3 ml/2850 E s.c./day for 7 days. Double dosage in case of previous radiation in the head and neck region. |
| Centre 2 | 16 | 3 | 182 | 100% | None | Fraxiparine 0.3 ml s.c. starting on the day before surgery | 3000 EH heparine iv | Fraxiparine 0.3 cc s.c. dd till 7 days postoperative. In case of previous radiation in the head and neck or vascular degenerative disease: heparin or liquemine, 15,000 I.U./day per 5 days. |
| Centre 3 | 25 | 2 | 254 | 95% | None | Fraxiparine s.c. | – | Fraxiparine s.c. |
| Centre 4 | 24 | 2 | 81 | 98% | DVT: 2× dd 0.6 ml faxiparin | Fraxiparin 0.3 ml s.c. starting on the day before surgery | – | Fraxiparine 0.6 cc s.c. 2 dd. |
| Centre 5 | 35 | 4 | 261 | 96% | None | DVT prophylaxis | – | – |
| Centre 6 | ? | ? | 245 | ? | None | ‘Routine DVT prophylaxis’ | – | – |
Other measures to prevent thrombosis
No specific studies on other non-pharmaceutical measures to prevent thrombosis after microvascular free-flap reconstruction were found. Measures taken include hydration with crystalloid fluids to maintain adequate blood volume and pressure .
The participating DHNCCs emphasized the importance of adequate preoperative vascular filling and the per- and postoperative hematocrit values ( Table 3 ). Two centres mentioned specifically that a perioperative systolic blood pressure of >120 mmHg has to be maintained. In one centre the patient is kept in a half-sitting position after the operation to stimulate venous return. Most of the DHNCCs strongly advise their patients to refrain from smoking prior to the operation.
| Preoperative | Peroperative | Postoperative | |
|---|---|---|---|
| Centre 1 | Smoking cessation advised | Good vascular filling | In prevention of edema body part with flap in supine position |
| Positive fluid balance for good vascular filling | |||
| No smoking for 3 weeks – good hematocrit values (0.30–0.35) | |||
| Centre 2 | – | Systolic blood pressure >120 mmHg | – |
| Intravasal volume has to be filled with HAES 40% | |||
| Centre 3 | Smoking cessation advised | – | – |
| Centre 4 | Smoking cessation advised | – | – |
| Centre 5 | Smoking cessation advised | Hematocrit values to max. 0.32 | Hematocrit values to max. 0.32 |
| Centre 6 | Smoking cessation advised | – | Penrose drain |
| Systolic blood pressure >100 < 160 | |||
| Supine position |
Results
Pharmacologic regimens: literature
No international guidelines were found for the use of anticoagulation in microvascular free-flap reconstruction in head and neck oncology.
Three RCTs could be included. D isa et al. compared three antithrombotic prophylaxis regimens in the head and neck region: first dextran 20 cc/h for 48 h, second dextran 20 cc/h for 120 h and third aspirin 325 mg/day for 120 h. These regimens were not significantly different in the incidence of thrombosis and subsequent flap survival. The groups using dextran as prophylaxis had a significantly higher rate of systemic complications . K houri et al. compared three types of intraluminal irrigating solution . In the first group, anastomoses were irrigated with a high dose of recombinant human tissue factor inhibitor (rhTFPI), in the second group a low dose was used and the third group used regular heparin. There were no significant differences in postoperative thrombosis rate. The authors concluded that the use of rhTFPI may only reduce the occurrence of postoperative complications such as hematomas . The third trial investigated the peroperative use of milrinone, a phosphodiesterase. The use of milrinone did not improve free-flap survival and had no significant influence on the occurrence of thrombosis .
A British survey on early postoperative care for free-flap head and neck reconstruction concluded that there was no consensus on the postoperative care regimen . As far as postoperative anticoagulation was concerned, only a minority of hospitals used standard postoperative anticoagulation . A survey on the postoperative use of dextran in microsurgery also concluded that there is a considerable variation in postoperative pharmacologic regimens . Table 1 summarizes the pharmacologic regimen used in nine large clinical series of head and neck reconstructions with free vascularized grafts . Low molecular weight heparin (LMWH) and heparin are used most frequently for anticoagulation. In addition, aspirin and prostaglandin are used.
