Aminocaproic acid administration is associated with reduced perioperative blood loss and transfusion in pediatric craniofacial surgery.

BACKGROUND: Severe blood loss is a common complication of craniofacial reconstruction surgery. The antifibrinolytic ε-aminocaproic acid (EACA) reduces transfusion requirements in children undergoing cardiac surgery and in older children undergoing spine surgery. Tranexamic acid (TXA), another antifibrinolytic with a similar mechanism of action, has been shown to reduce blood loss and transfusion requirements in children undergoing craniofacial surgery. However, TXA has been associated with an increase in post-operative seizures and is more expensive than EACA. There is currently little published data evaluating the efficacy of EACA in children undergoing craniofacial surgery. METHODS: This is a retrospective study of prospectively collected data from our craniofacial perioperative registries for children under 6 years of age who underwent anterior or posterior cranial vault reconstruction. We compared calculated blood loss, blood donor exposures, and post-operative drain output between subjects who received EACA and those who did not. RESULTS: The registry queries returned data from 152 subjects. Eighty-six did not receive EACA and 66 received EACA. The EACA group had significantly lower calculated blood loss (82 ± 43 vs. 106 ± 63 ml/kg, P = 0.01), fewer intraoperative blood donor exposures (median 2, interquartile range 1-2 vs. median 2, interquartile range 1-3; P = 0.02) and lower surgical drain output in the first post-operative 24 h (28 ml/kg vs. 37 ml/kg, P = 0.001) than the non-EACA group. CONCLUSION: In this analysis of prospectively captured observational data, EACA administration was associated with less calculated blood loss, intraoperative blood donor exposures, and post-operative surgical drain output.

Clinical care in craniofacial microsomia: a review of current management recommendations and opportunities to advance research.

Craniofacial microsomia (CFM) is a complex condition associated with microtia, mandibular hypoplasia, and preauricular tags. It is the second most common congenital facial condition treated in many craniofacial centers and requires longitudinal multidisciplinary patient care. The purpose of this article is to summarize current recommendations for clinical management and discuss opportunities to advance clinical research in CFM.

Population pharmacokinetics of epsilon-aminocaproic acid in infants undergoing craniofacial reconstruction surgery.

BACKGROUND: Understanding the clinical pharmacology of the antifibrinolytic epsilon-aminocaproic acid (EACA) is necessary for rational drug administration in children. The aim of this study is to determine the pharmacokinetics (PKs) of EACA in infants aged 6-24 months undergoing craniofacial reconstruction surgery. METHODS: Cohorts of six infants were enrolled sequentially to one of the three escalating loading dose-continuous i.v. infusion (CIVI) regimens: 25 mg kg(-1), 10 mg kg(-1) h(-1); 50 mg kg(-1), 20 mg kg(-1) h(-1); 100 mg kg(-1), 40 mg kg(-1) h(-1). Plasma EACA concentrations were determined using a validated high-performance liquid chromatography-tandem mass spectrometry assay. A population non-linear mixed effects modelling approach was used to characterize EACA PKs. RESULTS: Population PK parameters of EACA were estimated using a two-compartment disposition model with weight expressed as an allometric covariate and an age effect. The typical patient in this study had an age of 38.71 weeks and a weight of 8.82 kg. PK parameters for this typical patient were: pre-/postoperative plasma drug clearance of 32 ml min(-1) (3.6 ml kg(-1) min(-1)), inter-compartmental clearance of 42.4 ml min(-1) (4.8 ml min(-1) kg(-1)), central volume of distribution of 1.27 litre (0.14 litre kg(-1)), and peripheral volume of distribution of 2.53 litre (0.29 litre kg(-1)). Intra-operative clearance and central volume of distribution were 89% and 80% of the pre-/postoperative value, respectively. CONCLUSIONS: EACA clearance increased with weight and age. The dependence of clearance on body weight supports weight-based dosing. Based on this study, a loading dose of 100 mg kg(-1) followed by a CIVI of 40 mg kg(-1) h(-1) is appropriate to maintain target plasma EACA concentrations in children aged 6-24 months undergoing these procedures.

Lysis of antibody-coated cells by platelets.

Antibody-coated erythrocytes are lysed by murine C5- whole blood but not by plasma separated from such blood. The lytic activity has been shown to derive from platelets that attach to sensitized cells probably through membrane receptors for C3b. Whole blood or platelet-rich plasma (prp) obtained from mice that have been treated with purified cobra venom factor has little or no activity unless it is fortified with fresh C5- plasma. Lysis is observed only if the reactants are incubated at 37 degrees C and mechanical shaking is practiced, at least intermittently, throughout the period of incubation. Adherence of platelets and subsequent lysis are mediated by antibodies of a variety of immunoglobulin classes, including those that fail to mediate complement-dependent lysis. Platelet-mediated lysis is limited to cells to which the platelets adhere; 51Cr labeled, unsensitized cells that are mixed with prp and sensitized, unlabeled cells do not release 51Cr. Normal murine lymphoid cells and ascites tumor cells of mice, rats, and guinea pigs were apparently unaffected by sensitization and incubation with prp. However, because adherence of platelets to these sensitized cells was not observed, it is not clear whether the cells are resistant to the lytic action of platelets or whether the conditions of incubation were unfavorable for the attachment of platelets to the surfaces of nucleated cells. The significance of the lytic reaction described here is not known but may lie in antibody mediated release of microbicidal substances from platelets.

Heterogeneity of natural killer cells in the mouse.

Mice were treated with the bone-seeking isotope, 89Sr, cyclophosphamide, and short-term lethal irradiation in vivo, and murine spleen cells are treated with anti-Nk-1.2 plus complement (C) in vitro. Fresh spleen cell suspensions from the above groups and from beige and neonatal mice were subsequently tested for natural killer (NK) cell activity against a panel of lymphoid and nonlymphoid tumor cell target. NK cell reactivities against YAC-1, MPC-11, and Cl.18 tumors were markedly and consistently reduced in (a) mice treated with 89Sr, (b) spleen cells treated with anti-Nk-1.2 plus C, and (c) C57BL/6 bg/bg mice. In contrast, NK activities against FLD-3 and WEHI-164.1 tumors were usually normal in mice treated with 89Sr, in beige mutant mice, and in spleen cells after treatment with anti-Nk-1.2 antibody and C. It appears, therefore, that two major groups of NK cells exist in fresh mouse spleen cells suspensions. NK-A cells are marrow dependent, Nk antigen positive, and deficient in beige mice; these lyse YAC-1, MPC-11, and Cl.18 tumors. NK-B cells, which are responsible for the lysis of WEHI-164.1 and FLD-3, are Nk antigen negative, marrow independent, and unaffected by the bg/bg mutation. Other features of NK-B cells, suggest that these NK cells, although they share the characteristics mentioned above, differ among themselves especially with respect to age of maturation and susceptibility to cyclophosphamide and total body irradiation. The NK-B group may therefore induce subsets that remain to be defined.

Association between alleles of the transforming growth factor-alpha locus and the occurrence of cleft lip.

DNA samples from 100 patients with cleft lip with or without cleft palate (CL/P) were compared with those of 98 unaffected control individuals with respect to transforming growth factor alpha (TGFA) genotypes. Among the Caucasians in this population (83 CL/P, 84 controls), there was a significant difference in the restriction fragment length polymorphisms (RFLPs) observed after digestion with TaqI (chi 2 = 4.68, P = 0.03). The frequency of the C2 allele in the Caucasian CL/P population was 0.169, whereas that in the control group was 0.089. When the data for Caucasians, African-Americans, and Asians were examined jointly, the chi 2 value for the pooled sample was 5.08 (P = 0.02). This confirms the hypothesis of Ardinger et al. [1989, Am J Hum Genet, 45:348-353] that TFGA itself or a closely linked gene contributes to the development of CL/P in humans.

Phenotype of the fibroblast growth factor receptor 2 Ser351Cys mutation: Pfeiffer syndrome type III.

We present a patient with pansynostosis, hydrocephalus, seizures, extreme proptosis with luxation of the eyes out of the lids, apnea and airway obstruction, intestinal non-rotation, and severe developmental delay. His skeletal abnormalities include bilateral elbow ankylosis, radial head dislocation, and unilateral broad and deviated first toe. The phenotype of this patient is consistent with that previously reported in Pfeiffer syndrome type III, but is unusual for the lack of broad thumbs. Our patient most closely resembles the case described by Kerr et al. [1996: Am J Med Genet 66:138-143] as Pfeiffer syndrome type III with normal thumbs. Mutations in the genes for fibroblast growth factor receptors (FGFR) 1 and 2 have previously been seen in patients with Pfeiffer syndrome type I. The mutation identified in our patient, Ser351Cys in FGFR2, represents the first reported cause of Pfeiffer syndrome type III. An identical mutation was described once previously by Pulleyn et al., in a patient whose brief clinical description included cloverleaf skull, significant developmental delay, and normal hands and feet [Eur. J. Hum. Genet. 4: 283-291, 1996]. In our patient, previously performed single-strand conformation polymorphism analysis failed to detect a band shift; the mutation was identified only after independent sequence analysis.

Ocular and adnexal complications of unilateral orbital advancement for plagiocephaly.

Strabismus, ptosis, lateral canthal dystopia, nasolacrimal obstruction, and cranial nerve palsy were noted preoperatively in 32%, 21%, 14%, 12%, and 9% of 34 patients, respectively, undergoing ophthalmologic evaluation prior to unilateral orbital advancement for plagiocephaly. Thirty-two percent of the patients had normal preoperative ocular and adnexal examination results. Ptosis, strabismus, and amblyopia were frequently acquired postoperative abnormalities in 29%, 18%, and 18% of the patients, respectively. Forty-four percent of the patients had no new abnormalities following craniofacial surgery.

Crush injuries to the head in children.

Although the majority of head injuries in children and adults involve dynamic loading conditions, some patients suffer static loading. Static loading occurs when forces are applied slowly to the head, and it produces a much different pattern of injuries. Crush injuries are usually described in the context of industrial accidents, but in our experience, these injuries are not rare in children. We report a series of seven crush injuries in young children admitted during a period of 29 months and describe our experience in the evaluation and treatment of this complex entity. Patient ages ranged from 15 months to 6 years. In four cases, the child's head was run over by a motor vehicle backing up in a driveway or parking lot. In the three other patients, the static loading occurred when the child climbed or pulled on a heavy object, which then fell over with the child and landed on the child's head. One child with cervicomedullary disruption died shortly after his arrival at the hospital. The others showed varying degrees of soft tissue injury to the face and scalp, with Glasgow Coma Scale scores ranging from 7 to 15. Computed tomograms and magnetic resonance images showed multiple and often extensive comminuted calvarial fractures, as well as subarachnoid and parenchymal hemorrhages. All patients had basilar cranial fractures. There was one cervical spine injury but no major vascular injuries. One child had pituitary transection, four had cranial nerve palsies, and another developed a delayed cerebrospinal fluid rhinorrhea 18 months after injury. All children made good cognitive recoveries, with some having relatively mild fixed focal deficits.(ABSTRACT TRUNCATED AT 250 WORDS)

Temporal muscle microfixation in pterional craniotomies. Technical note.

Temporal muscle asymmetry is a common sequela of pterional craniotomies. The authors describe a simple technique of restoring the temporal muscle to its origin by microscrew fixation. This technique provides reliable preservation of temporal muscle bulk and function with little additional operating time and no compromise of operative exposure.

Effects of prophylactic antibiotics on wound infection after elective colon and rectal surgery: 1960 to 1980.

Wound infection continues to be a common complication of elective colon and rectal surgery. During the period from 1960 to 1980, 42 prospective, controlled prophylactic antibiotic trials were undertaken which addressed this problem. In this report we have analyzed these trials and compared them to all noncontrolled, prospective wound infection surveys and a representative sample of the retrospective surveys of the same period. From this analysis several conclusions have become apparent: (1) wound infection remains a common complication for which prophylactic antibiotics are generally effective, (2) the most effective agents are those with activity against anaerobic bacteria, (3) orally administered nonabsorbable antibiotics have little effect on reducing wound infection following these procedures, and (4) the optimal antibiotic regimen is yet to be found. The data do suggest, however, the more preferred regimens currently available as well as those worthy of further investigation.

The skeletal treatment of orbital hypertelorism.

Orbital hypertelorism, strictly defined as an increase in bony interorbital distance, is not itself an isolated syndrome, but is instead an anomaly that may occur as either part of a syndrome or malformation sequence. Evaluation of orbital hypertelorism and the various anomalies that accompany it is best performed by a multidisciplinary craniofacial team. The timing of surgery involves considerations of multiple variables, but when performed can offer marked cosmetic improvements. Equally important as the skeletal surgery is correction of the associated soft-tissue problems.

The craniofacial dysostoses: guidelines for management of the symmetric and asymmetric deformities.

Although great diversity marks the craniosynostoses, our experience related to that from other centers allows us to draw certain conclusions for their management. For the asymmetric synostoses, operative intervention should be carried out in infancy or early childhood. Although the unilateral approach is our preferred method, the bilateral approach can yield equally satisfactory results. Surgeons should, therefore, familiarize themselves with both methods and individualize for the given deformity. Mild symmetric (upper face) synostoses are best managed in infancy or early childhood, utilizing bilateral orbital advancement with the expectation that the need for additional major surgery will be at worst 50 per cent and likely significantly less. For moderate to severe synostoses, delaying major intervention to later childhood or adolescence maximizes the chance of obtaining a satisfactory result by a single procedure, either an extended LeFort III or monoblock advancement. Individualization of each case is essential, and the need for brain and eye protection or the psychologic needs of the patient may dictate a modification of the treatment guidelines. Patients and parents must be aware that growth and development subsequent to surgery is not entirely predictable, and there may be a need for a second major intervention at a subsequent time, despite these established guidelines.

Controversies in the management of pediatric facial fractures.

The treatment of pediatric maxillofacial fractures demands consideration of different factors than those in the adult and, therefore, a different therapeutic approach. We currently believe that certain principles in the management of these injuries can be outlined, recognizing that they may require modification as additional experience accumulates. These management principles are as follows: 1. Maintain a high index of suspicion for maxillofacial injury in the pediatric patient, especially when multiple trauma exists. 2. In addition to careful physical examination, utilize CT scanning on a routine basis, even for apparently trivial injuries. 3. Give consideration to observation only for minimally displaced fractures. 4. Respect the functional matrix and employ the least invasive surgical approach that will access the fracture and allow stable reduction. 5. Employ methods of fixation that adequately stabilize the facial skeleton without rigidly immobilizing long segments. 6. If rigid internal stabilization is necessary, in the form of conventional plate and screw fixation, give consideration to interval removal. 7. Microplates appear to provide enough stability so that their use can be advocated whenever possible. 8. Avoid the use of alloplastic materials, especially in the very young patient. 9. Use bone grafts sparingly, except in instances in which inlay reconstruction is necessary and onlay reconstruction is required to maintain soft-tissue support. 10. Be aware of the pediatric dentition and avoid iatrogenic injury to evolving teeth and tooth buds. Perhaps the most important principle of all is to document injuries and their method of treatment and to follow patients serially. This will allow further definition of fracture patterns and the effects of injury and its treatment on growth, thereby giving the surgeon a better understanding and ability to develop more concise treatment philosophies for the future.

Skeletal alterations as a basis for facial rejuvenation.

A slight decrease in overall facial bone bulk coupled with the increased soft-tissue expansion associated with aging produce effects that should be reversed in both the bone and soft tissue where possible. The changes are best done at the ledge areas: the supraorbital-temporal ridge areas, malar-midface, and chin mandible. However, the overall bone bulk may be increased in addition in the temporal fossae, in the infraorbital rim, at the lateral canthus, in the paranasal area, and at the alveolar ridges and dental areas. A combination of autogenous and synthetic materials is currently best, with synthetic materials most useful in the malar-midface, posterior mandibular, infraorbital, and paranasal areas. In the supraorbital ridge-temporal areas, it is a near equal choice between autogenous and synthetic materials. In the chin, the preferred method is by osteotomy using autogenous augmentation. The concept of increasing bone mass and decreasing expanded soft-tissue mass has application within the judgment of the surgeon coupled with the patient's desires. Subtle increases of bone mass to compensate for soft-tissue thinning as well as bone shrinkage, at the same time taking up lax soft tissue, can be done in conjunction with one another, effectively producing a three-layer face lift. The subperiosteal face lift is in reality an extended brow lift and can be used to enhance the brow-forehead area and the temporal, zygomatic, and paranasal areas. At the same time, the perioral, jowl, and submandibular regions must be treated by a combination of standard face lifting procedures and augmentation of the bone structures of the face.

Evaluation of facial skeletal aesthetics and surgical planning.

Proper surgical planning for aesthetic facial skeletal surgery requires of the surgeon not only intimate knowledge of available techniques but also an understanding of how and when to apply those techniques. To this end, proper facial form analysis is essential. In this introduction we have attempted to describe the elements of such an analysis, realizing that much remains to be learned about how the bone and soft tissue interact. In many ways the soft tissue--bone relations remain the unexplored area in aesthetic skeletal surgery. The further delineation of these relations by the use of anthropometry, laser light scanning, ultrasound, CT, and MRI remains an open area for investigation. The potential is enormous for using these data to study how bone and soft-tissue relationships combine to create facial form and how this form changes with both surgery and normal aging.

Avoiding pitfalls and managing complications of aesthetic contouring of the craniofacial skeleton.

Contouring of the facial skeleton has become applicable to a wide spectrum of patients. Although complications do occur, they now can be managed in a safe and predictable fashion. Moreover, it has been our experience that through increased use and attention to the tenets described in this article, the incidence of postoperative complications is significantly reduced.

Growth and survival of vascularized and nonvascularized membranous bone: an experimental study.

Although nonvascularized membranous bone grafts to the craniofacial skeleton demonstrate improved survival over similar grafts of endochondral origin, the comparative fate of vascularized membranous grafts is unknown. It is also unknown whether onlay membranous bone grafts in immature animals have the ability to grow. To examine these questions, a model was developed in New Zealand white rabbits in which a segment of the zygomatic arch was transferred to the subjacent mandible as either a vascularized or nonvascularized transfer. At harvest 16 weeks later, residual graft volume and bone architecture were analyzed. Results demonstrate no improved survival for vascularized membranous grafts in adult animals (n = 7), while in the immature animals (n = 6), growth of the vascularized bone transfers was documented. We conclude that in the majority of instances in craniofacial reconstruction, nonvascularized onlay membranous grafts are to be preferred. Specific instances for the use of vascularized transfers will be discussed.

The operative treatment of isolated craniofacial dysostosis (plagiocephaly): a comparison of the unilateral and bilateral techniques.

Both the safety and efficacy of the treatment of isolated craniofacial dysostosis (plagiocephaly) in infancy have been demonstrated. Opinions remain divided, however, as to the optimal type of procedure to be undertaken. In an attempt to answer this question, we have retrospectively evaluated a study population of 48 children operated on in infancy by either a unilateral or bilateral approach. Results of treatment at a minimal follow-up of 3 years were assessed based on preoperative and postoperative photographs and direct patient examination. Based on this retrospective comparison of the unilateral and bilateral approaches to the treatment of isolated craniofacial dysostosis, we conclude that (1) either approach as specifically outlined will give excellent results in the majority of patients, (2) there is no statistically significant difference in the results obtained by using either procedure, (3) in the majority of instances, less than ideal correction was manifested by contour irregularities evident in the temporal and/or lateral forehead region, and strict attention should be given to these areas in an attempt to further improve results, and (4) in those cases where significant protrusion is observed on the "normal side," a bilateral approach is preferable.

Lip reconstruction following Mohs' surgery: the role for composite resection and primary closure.

Surgical outcomes and patient satisfaction with composite resection and primary closure for the management of upper-lip defects following Mohs' surgery were evaluated. Twenty-seven patients underwent upper-lip reconstruction following Mohs' surgery from 1993 to 1997. Twelve of these patients were selected for this report based on adequate follow-up examinations and photographs. There were nine women and three men with a mean age of 46 years (range, 33 to 70 years). Eleven patients underwent Mohs' surgery for basal cell carcinoma and one patient for squamous cell carcinoma of the upper lip. The defects varied in size and location, often extending beyond a single aesthetic subunit. The reconstruction was performed an average of 7 days after Mohs' surgery (range, 1 to 23 days). In 50 percent of the cases, a full-thickness excision was performed, which included orbicularis oris and inner-lip mucosa. The functional results were graded as near normal to normal in all cases. There were no observed changes in oral continence, eating or speech. Two patients experienced numbness medial to the operative site, but this had no adverse affect on lip function. The aesthetic results were graded as very good to excellent in all cases. Eleven of the 12 patients were satisfied with their lip appearance and function. Conventional wisdom dictates that during reconstruction of upper-lip defects, one should attempt to maintain a majority of the uninvolved tissue for the best result. Although these techniques result in wound closure, they fail to consider lip aesthetics. By using a vertically oriented composite resection of the tipper lip with the additional resection of uninvolved tissue, normal lip architecture is maintained. In our experience, this results in a superior aesthetic and functional result.