Free Flap Reconstruction and Its Management in Sickle Cell Trait: Lessons Learned from a Case

Abstract

Oral cancers are amongst the most common cancers in the Indian subcontinent; in India alone, an estimated 1.2 lakh new patients were diagnosed with it. Reconstruction with free flaps slowly gained popularity over time to become the standard for care for treating large head and neck defects. Flap selection is a complex process; more specifically, the preoperative conditions of patients, the extent of the disease, and the resources available are critical considerations to consider when selecting the best reconstructive technique. It is very well established that certain parts of India, especially the tribal area of Central and southern India, have high prevalence of sickle cell trait (SCT) and sickle cell disease compared to the rest of the country. The sickle cell trait poses a potential increase in morbidity in the perioperative care due to surgical stress. Unfortunately, there are no published articles on the management of a free flap in a case of SCT. Here, in this article, we investigate the issues encountered during the perioperative care in a patient who undergone oral cavity composite resection with free fibula reconstruction. SCT screening must be undertaken mainly to identify, mitigate, and manage the adverse events in the perioperative period. The screening test is very inexpensive and has good sensitivity to detect the heterozygous and homozygous disease. We would recommend screening of all the patients hailing from high-risk endemic areas. The free flap in a case of sickle cell trait is not a contraindication, but a surgeon must understand the nuances in the management of complications in such case. Screening for sickle cell trait followed by perioperative blood transfusions, anticoagulation seems beneficial in a patient undergoing free flaps with sickle cell trait.

Introduction

Oral cancers are amongst the most common cancers in the Indian subcontinent; in India alone, an estimated 1.2 lakh new patients were diagnosed with it, with almost seventy-two thousand dying from it [1]. The standard treatment modality for oral cancers is surgery with or without reconstruction along with neck dissection followed by adjuvant therapy as per histopathology reports [2, 3]. With the ubiquity of microvascular surgery, harvesting free flaps has become popular in head and neck reconstruction. Reconstruction with free flaps slowly gained popularity over time to become the standard for care for treating large head and neck defects. Flap selection is a complex process; more specifically, the preoperative conditions of patients, the extent of the disease, and the resources available are critical considerations to consider when selecting the best reconstructive technique [4]. It is very well established that certain parts of India, especially the tribal area of Central and southern India, have high prevalence of sickle cell trait and sickle cell disease compared to the rest of the country [5, 6]. It is estimated that prevalence of sickle cell trait (SCT) is ranging between 10 and 30% in these so-called sickle cell belt [6]. The sickle cell disease leads to total free flap loss in The sickle cell trait poses a potential increase in morbidity in the perioperative care due to surgical stress. Unfortunately, there are no published articles on the management of a free flap in a case of SCT. Here, in this article, we investigate the issues encountered during the perioperative care in a patient who undergone oral cavity composite resection with free fibula reconstruction.

Case

A 44-year-old lady presented with right retromolar trigone growth, reformed gutka chewer; on biopsy, it was found to be a well-differentiated squamous cell carcinoma. Cross-sectional imaging by contrast-enhanced computerized tomography was done, which was suggestive of a T4b lesion—eroding ramus of mandible and extending to right retromolar trigone, masticator space (infranotch disease—masseter and medial pterygoid). As per multidisciplinary team meeting, the option of surgical excision and reconstruction with a free fibular osteomyocutaneous flap was given to the patient. Her routine blood investigations were done and found to be within normal limits. As part of her routine preoperative workup, screening sickling test was done, which came out to be positive. For further evaluation of this sickling and to determine the percentage of hemoglobin S, high-performance liquid chromatography (HPLC) was done (Table 1).

Table 1.

HPLC parameters

Hemoglobin	Percentage
Hb F	< 0.8
Hb Adult	67
Hb A2	3.4
Hb Sickle	24.3

A diagnosis of sickle cell trait was done as HbS levels were < 30%. Preoperative folic acid prophylaxis was started.

She undergone composite resection of buccal mucosa with right posterior segmental mandibulectomy (condyles sparing) with oncologically safe margins with right selective neck dissection (levels I–IV) and reconstruction with free fibular osteomyocutaneous flap reconstruction. The vascular anastomosis was done as follows: superior thyroid artery to peroneal artery, common facial vein with peroneal vein, and external jugular vein to vena comitans. Propofol was used for induction, along with fentanyl for pain, maintenance was done with inhalational sevoflurane and oxygen, nitrous oxide was not used in order to prevent sickling crisis [7], intraoperative hemodynamics were controlled with esmolol and dexmedetomidine infusion, and muscle relaxant used was vecuronium. Tracheostomy was performed; she was transferred to the intensive care following surgery and was kept sedated overnight. Neuromuscular reversal was done with glycopyrrolate and neostigmine. Piperacillin and tazobactam along with metronidazole were used for post-operative antibiotic coverage. Hyperdynamic circulatory state was maintained by using intravascular volume expanders—dextran at 40 ml/h, to prevent flap loss, with increased risk of thrombotic events.

While she was kept in the surgical intensive care unit, she was given prophylactic oxygen supplementation through T piece at 2.5L/min for the first two days to prevent any sickling due to reduced oxygen tension. Sulfa drugs and enzymatic combinations were avoided because of the sickle cell trait. Free flap monitoring was done with clinical examination to assess all four zones of free flap—flap color, turgidity, temperature, bleed on scratch (zones 1 and 2) assessment of flap and peripheral random blood sugar levels (zones 3 and 4) and handheld vessel Doppler (zone 1).

On post-operative day 1, the hemoglobin fell to 6.3 g% (preoperative—12.4 g%), disproportionate to the intraoperative blood loss of 850 ml. To prevent the flap loss due to low oxygen tension, a rigorous correction of anemia was done—a total of 3 units of packed cell volume was transfused over the next 2 days. Her post-transfusion (after 3rd PCV) hemoglobin was found to be 9.6 g%.

On post-operative day 5, she developed atrial fibrillation with heart rate of 180/min; during her stay in SICU, she was started on metoprolol and diltiazem to control the heart rate and rhythm. CHA2DS2-VASc scoring was done to assess the risk of stroke following atrial fibrillation—score -1, she was started on low molecular weight heparin (LMWH) and amiodarone as the patient was not yet ambulatory following the free fibula reconstruction. Sinus rhythm was maintained, and metoprolol changed to bisoprolol, and LMWH was changed to apixaban. Her hemoglobin also stabilized with hemoglobin on post-operative day 6 at 10.7 g% (Tables 2 and 3). Following which she was shifted out from intensive care to ward, the free fibula flap was healthy with good color and blood flow (Figs. 1 and 2).

Table 2.

Blood parameters during intensive care stay

	Preoperative	POD1	POD2	POD3	POD4	POD5
Hb (g/dl)	10.6	8.2	6.3	7.0	9.6	10.2
HCT (%)	33.2	25.9	19.4	21.5	29.5	30.8
TLC (WBC/microL)	10.85	18.43	12.71	13.56	14.92	10.71
PLT (/microL)	416	268	249	254	256	311
Urea (mg/dl)	18	24	17	20	15	16
Creatinine (mg/dl)	0.8	0.7	0.6	0.7	0.6	0.8
Sodium (mmol/L)	136	136	135	134	136	136
Potassium (mmol/L)	4.3	4.3	3.8	3.7	3.5	3.7
PT (sec)	10.2	11
INR	0.9	1

Table 3.

Average flap and peripheral blood glucose levels

Post-operative day	Flap RBS (mg/dl)	Peripheral RBS (mg/dl)	Ratio
1	138	148	0.93
2	160	156	1.03
3	118	150	0.79
4	90	113	0.80
5	139	126	1.10
6	99	114	0.87
7	98	110	0.89

Fig. 1.

External contour of free fibula

Fig. 2.

Intraoral cutaneous part of free fibula

She was started on oral liquids on day 9 and oral feed from day 10. Nasogastric tube was removed on day 10 (Fig. 3). Tracheostomy decannulation was done following videolaryngoscopic assessment on day 12. The patient was sent for adjuvant radiotherapy for T4 lesion. She was advised to maintain adequate hydration throughout the radiotherapy. Currently, the patient has completed her full course of radiotherapy (30#/60 Gy), without any treatment gaps or significant complications during radiation and with good locoregional disease control; Fig. 4 shows post-treatment 6-month follow-up photograph depicting early mucosalization of graft and excellent external contour.

Fig. 3.

Prevalence of HbS trait in India

Fig. 4.

6-month follow-up photograph showing early mucosalization and very good external contour

Discussion

Sickle cell disease (SCD) is one of the commonest abnormal hemoglobinopathies in the world occurring in along Equatorial Africa, Mediterranean countries, the Middle East, and various parts of India. In India it is usually found amongst the tribal populations. The Madhya Pradesh and Chhattisgarh states fall under the sickle cell belt, with an estimated prevalence of 11 to 30% [8]. The prevalence of sickle cell trait (HbAS) in Chhattisgarh was found to be 19.62% [9]. This high numbers usually warrants the need for routine preoperative screening for sickle cell disease and sickle cell trait.

Screening of HbS Trait and Disease

When should we screen for sickle cell trait? Screening for SCT in preoperative patients in endemic or high prevalence areas (Fig. 3) must be done using sickling test or solubility test as a part of the routine workup to mitigate complications in the perioperative period [10], especially for major surgeries involving extensive resections and microvascular reconstructions.

Sickling test: The solubility or sickling test is a remarkably simple and a cost-effective means to screen the sickle cell trait and disease amongst the patients. It has a high sensitivity 97.4 to 100% compared to HPLC [6]. The carrier state of HbS is termed as sickle cell trait, heterozygous state. The sickling test cannot differentiate between a heterozygous (trait) and homozygous (disease) states. Hence, a formal HPLC can be done if sickling test is found to be positive. Usually the HbS percentage in the blood ranges between 20 and 40% in a heterozygous state [11].

Role of folic acid in prophylaxis for heterozygous HbS: In sickle cell disease and trait, there is increased erythropoiesis, so it is postulated that these individuals are at higher risk of foliate deficiency [12]. It is also observed that the foliate prophylaxis reduces anemia [13] and vaso-occlusive crises or thrombotic events by preventing hyperhomocysteinemia [14]. Hence, it is recommended that the patient with HbS trait receive foliate prophylaxis.

Intraoperative Stressors and Choice of Antibiotics

Special precautions must be taken to prevent the perioperative stress that would trigger vaso-occlusive crisis. Intracellular dehydration is a very well-established factor leading to HbS polymerization; prolonged fasting must be avoided, in case of major head and neck surgeries—intravenous fluids is mandatory. There is evidence that hypotonic fluids may help prevent HbS polymerization [15], although strict fluid electrolyte balance is absolutely necessary to prevent pulmonary edema.

In routine and minor procedures, oxygen supplementation is not mandatory [16]. In select cases with major resections and microvascular reconstructions, the oxygen supplementation may be deemed necessary, with strict monitoring by pulse oximetry, although there is a lack of high-quality evidence supporting this.

The routine use of low molecular weight dextran 40 to curtail the thrombotic events in the free flaps is not necessary as the benefits outweigh the risk [17, 18]. Dextran 40 was used in this case as the sickle cell trait is a high-risk prothrombotic disease [19] and also helps in maintaining the intravascular volume. The clinicians must understand the risks associated with the dextran 40, before they venture out to use it. Preoperative Transfusion in Sickle Cell Disease Study Group recommend that the perioperative hemoglobin goal must be 10 g% and HbS levels of < 30%; this would lead to lesser rates of perioperative complications [20]. The goals of anesthesia in sickle cell must be to minimize exposure to hypoxemia, hypercapnia, acidosis, hypothermia, and hypovolemia during surgery. Higher antibiotics and antipseudomonal antibiotics can be used when prolonged stay in the intensive care is needed; there are some reports of higher chances of developing pseudomonas infection in sickle cell disease [21].

Methods of Flap Selection and Ischemia

Free flap selection is a complex process per se; the sickle cell trait adds an extra weight to it. Usually pedicled flaps are considered a safer option when HbS is around 30%, as it would lead to better outcomes [22]. This patient required a composite free flap for reconstruction of defect. Free fibula myocutaneous flap was the obvious choice for managing this defect. There is common doctrine tourniquet application to a limb usually establishes the perfect circumstances for HbS polymerization by the virtue of stasis, hypoxia, and acidosis in the distal limb. Sickle cell disease is a known relative contraindication to microvascular surgery due to the risk of anastomotic thrombosis (33%) and partial or total flap loss (22% and 11% respectively) [23]. SCT has been linked with increased risk of venous thromboembolism, splenic infarcts, sudden exertional deaths, hyposthenia, and hematuria affecting graft viability and producing post-operative complications [24]. A scarcity of published data with regard to microvascular free flap viability and outcomes in SCT was seen with no published data found on the use of free flap in head and neck malignancy in a SCT patient. Nonetheless, as shown in a review of a relatively few scientific research, tourniquets can be used safely in most sickle cell patients with proper perioperative management [25].

Atrial Fibrillation and Sickle Cell Trait

The REGARDS cohort by Douce and colleagues showed that sickle cell trait was associated with 1.32 times increased odds of atrial fibrillation independent of all measured risk factors. The evidence provided is inconclusive with the mechanism unknown. They concluded that the sickle cell trait may increase the risk of atrial fibrillation [26].

Conclusion

Sickle cell trait is a common benign condition which needs to be screened routinely in patients posted for major surgeries with microvascular reconstructions, mainly to identify, mitigate, and manage the adverse events in the perioperative period. The screening test is very inexpensive and has good sensitivity to detect the heterozygous and homozygous disease. We would recommend screening of all the patients hailing from high-risk endemic areas. The free flap in a case of sickle cell trait is not a contraindication, but a surgeon must understand the nuances in the management of complications in such case. Screening for sickle cell trait followed by perioperative blood transfusions, anticoagulation seems beneficial in a patient undergoing free flaps with sickle cell trait.