Pediatric Mandibular Fracture Management: Intraoperative Thermoplastic Splint Fabrication and Circummandibular Wires, without Maxillomandibular Fixation.

Management of mandibular fractures often involves the use of maxillomandibular fixation (MMF) to attain immobility of the fractured segments. This can be used as a primary treatment modality or as an adjunct in fracture management. This technique, however, has its drawbacks due to the great burden of care imposed on patients. In the following case, fixation of a pediatric open mandibular body fracture was attained without the use of MMF, and bone union was achieved. Due to age, safety concerns, long-distance travel, and parent's preference, the routine management of this type of fracture with MMF using piriform aperture drop wires and circummandibular wires was not done. Instead, the fracture was reduced, and an intraoral mandibular impression was taken in the operating room, which was used to create a stone model. A 2-mm acrylic splint was designed and fabricated from the stone model, and two circummandibular wires were placed. The wires were tightened over the acrylic splint to achieve stabilization of the mandibular reduction. At 4 weeks postoperatively, the splint was removed, and the patient was maintained on a soft diet. At 6 weeks, bone union was appreciated clinically by immobility of the mandibular segments, and the patient was advanced to a regular diet. Occlusion was corrected to premorbid state by clinical findings and 6 months postoperative imaging. This technique represents an effective approach in managing pediatric mandibular fractures when MMF cannot be used.

Distraction Osteogenesis for Frontosphenoidal Craniosynostosis: a Novel Surgical Treatment Modality of a Rare Suture Fusion.

Frontosphenoidal craniosynostosis (FSC) is a rare premature fusion of the frontosphenoidal suture that results in anterior plagiocephaly. When associated with severe cranial deformity, surgical treatment is beneficial. All previously reported cases of FSC correction have utilized fronto-orbital remodeling and advancement to achieve improved anatomy and increased intracranial volume. For patients with isolated synostosis deformities, we believe that distraction osteogenesis can be a viable option, with the additional benefit of quicker operating time, shorter hospital stays, and less irregularity in final head contour. This case illustrates the feasibility of using distraction osteogenesis in the management of FSC.

What to do with an incidental finding of a fused sagittal suture: a modified Delphi study.

OBJECTIVE: As many as 5% of normocephalic children may have a prematurely fused sagittal suture, yet the clinical significance and best course of management of this finding remain unclear. Providers in the Synostosis Research Group were surveyed to create a multicenter consensus on an optimal treatment and monitoring algorithm for this condition. METHODS: A four-round modified Delphi method was utilized. The first two rounds consisted of anonymous surveys distributed to 10 neurosurgeons and 9 plastic surgeons with expertise in craniosynostosis across 9 institutions, and presented 3 patients (aged 3 years, 2 years, and 2 months) with incidentally discovered fused sagittal sutures, normal cephalic indices, and no parietal dysmorphology. Surgeons were queried about their preferred term for this entity and how best to manage these patients. Results were synthesized to create a treatment algorithm. The third and fourth feedback rounds consisted of open discussion of the algorithm until no further concerns arose. RESULTS: Most surgeons preferred the term "premature fusion of the sagittal suture" (93%). At the conclusion of the final round, all surgeons agreed to not operate on the 3- and 2-year-old patients unless symptoms of intracranial hypertension or papilledema were present. In contrast, 50% preferred to operate on the 2-month-old. However, all agreed to utilize shared decision-making, taking into account any concerns about future head shape and neurodevelopment. Panelists agreed that patients over 18 months of age without signs or symptoms suggesting elevated intracranial pressure (ICP) should not undergo surgical treatment. CONCLUSIONS: Through the Delphi method, a consensus regarding management of premature fusion of the sagittal suture was obtained from a panel of North American craniofacial surgeons. Without signs or symptoms of ICP elevation, surgery is not recommended in patients over 18 months of age. However, for children younger than 18 months, surgery should be discussed with caregivers using a shared decision-making process.

Modifications to the WHISTLE Flap Procedure for Correction of Secondary Cleft Lip Deformities.

Background: The whistle deformity, a deficiency of tissue in the central upper lip, is a consequential outcome of primary cleft lip repair. Among multiple described reconstructive options, the wide-hinged island swing transposition labial enhancement (WHISTLE) flap procedure by Grewal et al has been shown to be a reliable technique that restores the continuity of the orbicularis oris muscle and creates a more natural appearing tubercle and central lip element. This article aims to refine the WHISTLE flap procedure with the addition of tailored mucomuscular flaps and an upper lip-lengthening mucosal Z-plasty. Methods: A total of 11 patients with a whistle deformity were examined. All underwent the WHISTLE flap procedure with tailored mucomuscular flaps and a mucosal Z-plasty. The patients were followed for a period of from 6 to 51.5 months. Pre- and postoperative photographs were used for objective outcome comparison. Results: From 2018 to 2023, a total of 11 patients with a whistle deformity were included in the final cohort, comprised four bilateral and seven unilateral cleft lips. Ten cases (90.1%) resulted in satisfactory postoperative cosmetic appearance and did not require further interventions. A single patient with a significant preoperative discrepancy between the upper and lower lip volumes had a postoperative residual deformity. None of the patients demonstrated any functional deficits associated with the procedure. Conclusions: The WHISTLE flap procedure with the proposed individual tailoring of the mucomuscular flap and Z-plasty for mucosal scar lengthening has excellent cosmetic outcomes and can be considered as the primary treatment modality in most patients with a whistle deformity.

Early Results on the Efficacy of Demineralized Bone Matrix, Bone Morphogenic Protein, and Freeze-dried Bone Chips in Alveolar Cleft Repair.

Background: Conventional treatment for alveolar cleft repair is done using autologous iliac crest alveolar bone graft (ABG). However, this method may not be ideal in all patients. Analysis of the efficacy of a mixture of demineralized bone matrix (DBX), bone morphogenic protein (rhBMP-2), and freeze-dried bone chips (FDBC) as an alternative for alveolar cleft repair was performed. Methods: Consecutive patients from August 2019 to June 2022 undergoing early alveolar cleft repair, concomitant hard palate and alveolar cleft repair, secondary alveolar cleft repair, and regrafting from a previously failed ABG were analyzed. Computed tomography scans were performed to evaluate graft take at least 6 months postoperatively. Images were reviewed and scored. Alveolar graft height and graft thickness were recorded. A standardized scoring system was developed, with a score of 0 representing no graft take and 3 representing best possible graft take. Results: Fifty-five consecutive alveolar clefts (43 patients) were identified as having undergone ABG and satisfied all the other inclusion criteria. Of these, 29 underwent first time ABG and 26 underwent redo ABG. The mean graft height and graft thickness recorded for all clefts was 2.2 and 2.0, respectively. Conclusions: Early results evaluating the efficacy of ABG using DBX, rhBMP-2, and FDBC show feasibility in regard to both graft height and thickness when using a maxillary computed tomography scan to measure the bone graft take. These results suggest that DBX, rhBMP-2, and FDBC may act as a versatile bone graft material in cleft care, although further studies are needed to determine long-term outcomes.

Novel Custom Maxillary Disimpaction Splint.

LeFort I, II, and III osteotomies are commonly used in complex craniofacial reconstruction. Patients requiring these procedures typically have a craniofacial cleft, other congenital craniofacial deformities, or severe facial trauma. Both the cleft and traumatized palate have poor bony support, which leads to possible complications when the disimpaction forceps are used during the downfracture of the maxilla. Such potential complications include trauma or formation of a fistula of the palatal, oral, or nasal mucosa; trauma to adjacent teeth; and fracture of the palate and alveolar bone. To help prevent these complications, we developed a custom disimpaction splint. The splint is designed to cover the palate and occlusal surfaces to increase retention and minimize splint movement during the maxillary downfracture portion of the surgical procedure. The base of the splint is fabricated from a two-layered biocryl material, and the palatal area is built with soft-cushion rebase material. This allows for a stable grip of the disimpaction forceps blades and provides protective coverage of the cleft, traumatized palate, or alveolar bone graft site during the downfracture. The custom maxillary disimpaction splint has been routinely used in our clinic from September 2019 to the present for LeFort osteotomies in patients with a compromised primary palate. No surgical complications related to the maxillary downfracture have been noted during this period of time. We conclude that the routine use of a custom maxillary disimpaction splint can result in improved outcomes and decreased complications of LeFort osteotomy procedures in patients with cleft and traumatized palate.

Multimodal Management of Facial Keloid with Tissue Expansion, Excision, and Injection of 5-FU and Triamcinolone.

Keloids are benign, fibroproliferative dermal growths that occur in response to injury of the skin. These hypertrophic scars can cause pain and discomfort and have been associated with negative effects on social well-being, prompting physicians to seek effective treatment modalities with minimal risk of recurrence. Although surgical excision of the keloid initially removes the scar tissue, surgery alone triggers a fibroproliferative response similar to the initial insult, resulting in a high recurrence rate. Thus, a multimodal approach may be most appropriate when surgery is indicated to limit recurrence. We present the successful treatment of recalcitrant keloid formation of the face that was treated with tissue expansion, excision, and intralesional triamcinolone and 5-flurouracil injections.

Modified Antia-Buch Flap Incorporating an Extended Temporal Scalp Incision.

The Antia-Buch flap is a popular reconstructive method for full-thickness ear defects involving the helical rim. However, scaphal or conchal resection is often required to prevent ear distortion. Noel et al described a modified technique to the Antia-Buch flap, which includes an incision in the temporal scalp and complete detachment of the preauricular helical root to increase mobility of the flap. Since then, no studies have reported on the use of this modification. We report our experience in implementing Noel et al's modification of the Antia-Buch flap for helical rim defects. Methods: The modified technique differs from the original Antia-Buch flap by completely detaching the root of the helix and adding a vertical incision to the temporal scalp to increase mobility of the flap. No scaphal resection is necessary. After complete elevation of the flaps, the flaps are advanced and inset toward each other followed by closure. Results: In our practice, 10 patients have been treated with Noel et al's modification to the Antia-Buch flap. In each of these patients, acceptable reconstruction of the helical rim was able to be achieved. All the patients were pleased with their reconstructive outcome and ear anatomy was able to be successfully maintained. Conclusions: The modified Antia-Buch flap has shown to be an excellent method for large, helical rim defects, creating versatility by adding the temporal scalp incision. Our outcomes with Noel et al's modification to the original Antia-Buch flap support this method as a versatile technique for wide full-thickness helical rim defects.

A Simple Surgical Solution for Functional Improvement of Deforming Vascular Malformations with Lip Involvement.

The management of large, deforming facial arteriovenous malformations (AVMs) can be a daunting clinical challenge for patients and surgeons. Many patients delay treatment due to fear of surgical intervention and concern for unfavorable cosmetic outcomes. Delaying treatment can lead to soft-tissue hypertrophy. Occasionally, facial AVMs can also present with lip involvement, necessitating surgical intervention. A major potential issue regarding AVMs managed with surgical excision is excessive bleeding due to the enlarged dermal vascular plexus. Here, we present a simple surgical technique used to manage deforming AVMs involving the lips. A 32-year-old man with Sturge-Weber syndrome and a 72-year-old man with AVMs of the left face presented to clinic for management. The malformations involved the lips in both patients. Both patients had constant drooling and difficulty eating and talking, in addition to aesthetic concerns. They both underwent surgical excision of the redundant tissue with minimal undermining, advancement flaps, and layered closure. Minimal undermining allowed successful removal of the AVMs and redundant tissue without excessive blood loss and allowed healing without complications. Both patients had significant improvement in eating and talking without drooling. Aesthetically, satisfactory outcomes were maintained at 1-year follow-up appointments. Removal of AVMs while minimizing blood loss can be a challenging endeavor. Here, we have presented a successful, effective technique for restoring both form and function in patients with AVMs involving the lips, with good long-term results.

Masseter-to-facial nerve transfer for facial nerve reanimation.

Smooth symmetric facial muscle function is important for social interactions. When lesions of the facial nerve occur, achieving complete restoration of balanced and spontaneous facial function can be challenging. In this video, the authors demonstrate the surgical details and long-term follow-up of a masseter-to-facial nerve transfer in a 3-year-old girl who had insidious onset of a left facial palsy due to a facial nerve schwannoma. After resection, she underwent distal nerve repair with a masseter-to-zygomatic branch transfer. She demonstrated decreased lagophthalmos and good activation and excursion on the left side with near symmetry to the right side, but lacked left frontalis function. The video can be found here: https://stream.cadmore.media/r10.3171/2022.9.FOCVID22107.

Multidisciplinary Presurgical Education: Clinical Impact on Children With Orofacial Clefts Undergoing Maxillary Distraction via Rigid External Distraction.

OBJECTIVE: Treatment of severe maxillary hypoplasia is commonly addressed via distraction osteogenesis with a rigid external device (RED). While effective, this method can be socially stigmatizing in an already vulnerable patient population. To prepare children and their caregivers for life with a RED and decrease peri-operative anxiety, we instituted a multidisciplinary pre-surgical education session (MPES). This educational team involves our cleft care coordinator, child life specialist, orthodontist and plastic surgeon 2 weeks prior to surgery. We reviewed the impact of this intervention by examining clinical outcomes before and after its implementation. DESIGN: From February 2017 to February 2020, a retrospective chart review was performed to include patients with orofacial clefts and maxillary hypoplasia who underwent maxillary distraction osteogenesis with RED at our center before (28 patients) and after (29 patients) the implementation of MPES. RESULTS: MPES was associated with a significantly shorter length of stay compared to controls who did not receive MPES (3.6 vs 3.1 days, p < 0.03) and significantly decreased usage of inpatient narcotic pain medication compared to controls (16.8 morphine equivalents vs 31.8 morphine equivalents, p < 0.02). Our intervention also demonstrated a trend towards decrease in minor complications but did not achieve statistical significance p = 0.32). CONCLUSIONS: Multidisciplinary presurgical education is a beneficial adjunct in the care of patients with orofacial clefts and maxillary hypoplasia undergoing maxillary advancement with a RED.

A Custom Stabilizing Splint for the Management of BLCP with Protruding Premaxilla.

A severely protruding premaxilla in a patient with bilateral cleft lip and palate prevents functional closure of the orbicularis oris muscle and acceptable reconstruction of the nasolabial components during primary cheiloplasty. This is typically corrected with vomerine osteotomy and premaxillary setback, followed by cheiloplasty and rhinoplasty. Due to the risk of vascular compromise to the prolabium and premaxillary segment, the lip and nose repair is often staged after the vomerine osteotomy and premaxillary setback has healed. Stabilizing the premaxillary segment to allow adequate healing has been a topic of interest. Several methods have been described, but each is associated with varying degrees of compromise of the blood supply to the premaxilla. To combat this, the authors created a custom oral splint that effectively maintained the position of the premaxilla with minimal impingement of the blood supply. The authors present two cases in which a two-stage premaxillary setback with a custom-stabilizing oral splint was performed, followed by primary cheiloplasty and rhinoplasty in an age-appropriate and delayed presentation of bilateral cleft lip and palate and protruding premaxilla.

Frontofacial Reconstruction Technique Modification With Preservation of Blood Supply to the Monobloc Segment.

ABSTRACT: Craniosynostosis syndromes, including Apert Syndrome, Pfeiffer Syndrome, and Crouzon Syndrome, share similar phenotypes, including bicoronal craniosynostosis, midface hypoplasia, hypertelorism, and exorbitism. The standard surgical treatment for these craniofacial abnormalities is monobloc osteotomy with distraction osteogenesis. Complications of this technique include the failure of osteogenesis or resorption of the frontal bone. The authors propose an alternative surgical technique with a frontal arch in continuity with the midface segment to ensure vascularization to anterior and posterior borders of distraction. A case report of an 8-year-old female patient with Apert Syndrome is reported using our technique. Our frontal arch monobloc distraction procedure preserves blood supply to a cranial component of the monobloc segment site that becomes the anterior portion of distraction rather than with the traditional devascularized frontal bone flap. This technique modification should improve osteogenesis outcomes by preventing resorption or failure of bone formation.

Mandibular Myofibroma and Severe Trismus: A Complex Case and Review of Complications.

A female child was investigated for insidious onset of temporomandibular joint dysfunction and trismus in the setting of a mandibular myofibroma. Myofibromas, benign mesenchymal neoplasms composed of spindle cells, are rarely found in the oral cavity, most commonly in the mandible. These lesions are historically described as indolent with a high cure rate and minimal recurrence rates following surgical resection. The patient initially presented with concerns regarding snoring, retrognathia, and jaw ankylosis, as well as a history of trouble latching as an infant but without obvious physical deformities. Imaging revealed a large expansile lytic mass of the mandible, but no temporomandibular joint involvement; surgical biopsy evidenced myofibroma, and the lesion was resected. Over the course of disease, the lesion continued to expand, and the patient's maximal incisal opening continued to decrease despite conservative management with jaw physiotherapy; eventually she could not open her mouth despite the absence of joint involvement. Re-exploration along with formal jaw physiotherapy was achieved and optimal jaw opening was maintained. Myofibromas are rare benign desmoid tumors that can present anywhere in the body in solitary and multicentric forms, and previously did not present significant challenges to surgical and medical management. Tumors of the mandible may present with trismus and soft tissue ankylosis, which can mimic temporomandibular joint dysfunction in the absence of joint involvement. Physical therapy, rehabilitation, and soft tissue contracture release are key to management and improving outcomes in oral cancer patients, regardless of tumor pathology.

Simultaneous Closure of the Cleft Alveolus and Hard Palate with Concomitant Bone Grafting.

Cleft repair has been in constant evolution since its inception. Conventional repair of the cleft hard palate involves closure of nasal and oral mucosa without bony reconstitution. In many instances, this approach is adequate, but, particularly in complete clefts, the lack of bony support can lead to collapse of the maxillary arch, dental crowding, and posterior cross-bite. To address these shortcomings, our institution performs a two-staged palatoplasty with concomitant bone grafting of the alveolus and hard palate in the second stage. A retrospective review of children who underwent a two-staged palatoplasty at our institution was performed. These patients' records and images were reviewed for complications and changes in maxillary morphology. Fourteen patients with complete clefts had a two-staged palatoplasty with bone grafting in the second stage. The mean age at surgery was 37.5 months, and the mean follow-up was 16 months. One patient had resorption of the alveolar bone graft requiring additional bone grafting. The remaining patients were without complications and had good consolidation of the bone graft on follow-up imaging. Our early results support that there is a low complication rate (7% regrafting) in those patients who underwent bone grafting at the time of cleft palate repair with early evidence of bony consolidation on imaging and clinical examination. Wide exposure during the repair allows complete grafting of the maxillary bony deficit, which is not possible with traditional alveolar cleft repair and may alleviate the shortcoming of soft-tissue closure only. Future study is necessary to determine long-term outcomes.

Severe Cherubism Treated with Curettage, Osteotomy, and Bony Repositioning: A Case Series of Three Patients.

Cherubism is a rare, autosomal dominant condition characterized by the replacement of medullary bone by fibro-osseous lesions, predominantly in the bilateral maxillae and/or mandibles. The clinical presentation of cherubism can vary widely, from clinically undetectable to severe facial disfigurement. Although there are no established management guidelines for this condition, conservative management with observation is typically favored in most cases due to the possibility of spontaneous regression following puberty. In this article, we present three cases of moderate to severe cherubism managed with early surgical intervention utilizing curettage and osteotomy followed by bony repositioning. We aimed to show the feasibility and safety of this minimally invasive surgical technique in the management of moderate to severe cases of cherubism to provide improvement in patient quality of life, aesthetics, and function while also possibly mitigating the need for later reconstructive surgery.

Management of Large Pediatric Wound Defects Using a Continuous External Tissue Expander.

Both internal and external tissue expanders take advantage of the innate adaptive mechanisms the skin exerts in response to mechanical tension, known as the stress-relaxation phenomenon. Internal tissue expander use is time-consuming and can be complicated by infection and extrusion. In this case series, continuous external tissue expanders used to manage large pediatric wounds were assessed. Fourteen patients (ages: 4 days to 17 years) with large wounds underwent continuous external tissue expansion intraoperatively. The success of wound closure was assessed. In addition, the size of the patient's wounds, duration of device application, and postoperative complications were evaluated. The continuous external tissue expander was applied to wound sizes ranging from 14.7 to 560 cm2 for 5 to 10 days until the wound was amenable for direct closure. In 11 of the 14 patients, delayed primary closure was achieved. The device significantly reduced the wound sizes of the remaining three cases (average 80% size reduction). There was no incidence of wound dehiscence or infection. This case series demonstrates the benefit of the continuous external tissue expansion in managing pediatric wounds that would not otherwise be amenable to primary closure. The method allows for timely closure with limited risk of infection or extrusion, and should be in the armamentarium of reconstructive plastic surgeons.

Preoperative imaging patterns and intracranial findings in single-suture craniosynostosis: a study from the Synostosis Research Group.

OBJECTIVE: The diagnosis of single-suture craniosynostosis can be made by physical examination, but the use of confirmatory imaging is common practice. The authors sought to investigate preoperative imaging use and to describe intracranial findings in children with single-suture synostosis from a large, prospective multicenter cohort. METHODS: In this study from the Synostosis Research Group, the study population included children with clinically diagnosed single-suture synostosis between March 1, 2017, and October 31, 2020, at 5 institutions. The primary analysis correlated the clinical diagnosis and imaging diagnosis; secondary outcomes included intracranial findings by pathological suture type. RESULTS: A total of 403 children (67% male) were identified with single-suture synostosis. Sagittal (n = 267), metopic (n = 77), coronal (n = 52), and lambdoid (n = 7) synostoses were reported; the most common presentation was abnormal head shape (97%), followed by a palpable or visible ridge (37%). Preoperative cranial imaging was performed in 90% of children; findings on 97% of these imaging studies matched the initial clinical diagnosis. Thirty-one additional fused sutures were identified in 18 children (5%) that differed from the clinical diagnosis. The most commonly used imaging modality by far was CT (n = 360), followed by radiography (n = 9) and MRI (n = 7). Most preoperative imaging was ordered as part of a protocolized pathway (67%); some images were obtained as a result of a nondiagnostic clinical examination (5.2%). Of the 360 patients who had CT imaging, 150 underwent total cranial vault surgery and 210 underwent strip craniectomy. The imaging findings influenced the surgical treatment 0.95% of the time. Among the 24% of children with additional (nonsynostosis) abnormal findings on CT, only 3.5% required further monitoring. CONCLUSIONS: The authors found that a clinical diagnosis of single-suture craniosynostosis and the findings on CT were the same with rare exceptions. CT imaging very rarely altered the surgical treatment of children with single-suture synostosis.

Management of sagittal synostosis in the Synostosis Research Group: baseline data and early outcomes.

OBJECTIVE: Sagittal synostosis is the most common form of isolated craniosynostosis. Although some centers have reported extensive experience with this condition, most reports have focused on a single center. In 2017, the Synostosis Research Group (SynRG), a multicenter collaborative network, was formed to study craniosynostosis. Here, the authors report their early experience with treating sagittal synostosis in the network. The goals were to describe practice patterns, identify variations, and generate hypotheses for future research. METHODS: All patients with a clinical diagnosis of isolated sagittal synostosis who presented to a SynRG center between March 1, 2017, and October 31, 2019, were included. Follow-up information through October 31, 2020, was included. Data extracted from the prospectively maintained SynRG registry included baseline parameters, surgical adjuncts and techniques, complications prior to discharge, and indications for reoperation. Data analysis was descriptive, using frequencies for categorical variables and means and medians for continuous variables. RESULTS: Two hundred five patients had treatment for sagittal synostosis at 5 different sites. One hundred twenty-six patients were treated with strip craniectomy and 79 patients with total cranial vault remodeling. The most common strip craniectomy was wide craniectomy with parietal wedge osteotomies (44%), and the most common cranial vault remodeling procedure was total vault remodeling without forehead remodeling (63%). Preoperative mean cephalic indices (CIs) were similar between treatment groups: 0.69 for strip craniectomy and 0.68 for cranial vault remodeling. Thirteen percent of patients had other health problems. In the cranial vault cohort, 81% of patients who received tranexamic acid required a transfusion compared with 94% of patients who did not receive tranexamic acid. The rates of complication were low in all treatment groups. Five patients (2%) had an unintended reoperation. The mean change in CI was 0.09 for strip craniectomy and 0.06 for cranial vault remodeling; wide craniectomy resulted in a greater change in CI in the strip craniectomy group. CONCLUSIONS: The baseline severity of scaphocephaly was similar across procedures and sites. Treatment methods varied, but cranial vault remodeling and strip craniectomy both resulted in satisfactory postoperative CIs. Use of tranexamic acid may reduce the need for transfusion in cranial vault cases. The wide craniectomy technique for strip craniectomy seemed to be associated with change in CI. Both findings seem amenable to testing in a randomized controlled trial.

Optimal Dosing of Prophylactic Enoxaparin after Surgical Procedures: Results of the Double-Blind, Randomized, Controlled FIxed or Variable Enoxaparin (FIVE) Trial.

BACKGROUND: The accepted "one-size-fits-all" dose strategy for prophylactic enoxaparin may not optimize the medication's risks and benefits after surgical procedures. The authors hypothesized that weight-based administration might improve the pharmacokinetics of prophylactic enoxaparin when compared to fixed-dose administration. METHODS: The FIxed or Variable Enoxaparin (FIVE) trial was a randomized, double-blind trial that compared the pharmacokinetic and clinical outcomes of patients assigned randomly to postoperative venous thromboembolism prophylaxis using enoxaparin 40 mg twice daily or enoxaparin 0.5 mg/kg twice daily. Patients were randomized after surgery and received the first enoxaparin dose at 8 hours after surgery. Primary hypotheses were (1) weight-based administration is noninferior to a fixed dose for avoiding underanticoagulation (anti-factor Xa <0.2 IU/ml) and (2) weight-based administration is superior to fixed-dose administration for avoiding overanticoagulation (anti-factor Xa >0.4 IU/ml). Secondary endpoints were 90-day venous thromboembolism and bleeding. RESULTS: In total, 295 patients were randomized, with 151 assigned to fixed-dose and 144 to weight-based administration of enoxaparin. For avoidance of under anticoagulation, weight-based administration had a greater effectiveness (79.9 percent versus 76.6 percent); the 3.3 percent (95 percent CI, -7.5 to 12.5 percent) greater effectiveness achieved statistically significant noninferiority relative to the a priori specified -12 percent noninferiority margin (p = 0.004). For avoidance of overanticoagulation, weight-based enoxaparin administration was superior to fixed-dose administration (90.6 percent versus 82.2 percent); the 8.4 percent (95 percent CI, 0.1 to 16.6 percent) greater effectiveness showed significant safety superiority (p = 0.046). Ninety-day venous thromboembolism and major bleeding were not different between fixed-dose and weight-based cohorts (0.66 percent versus 0.69 percent, p = 0.98; 3.3 percent versus 4.2 percent, p = 0.72, respectively). CONCLUSION: Weight-based administration showed superior pharmacokinetics for avoidance of underanticoagulation and overanticoagulation in postoperative patients receiving prophylactic enoxaparin. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.