- Email: [email protected]
Present-day dune environment dynamics on the coast of the Świna Gate Sandbar (Polish West coast)
CRANIOMAXILLOFACIAL DEFORMITIES/COSMETIC SURGERY
A Prospective, Randomized, Double-Blind, Placebo-Controlled Clinical Trial Comparing the Efficacy of Systemic Enzyme Therapy for Edema Control in Orthognathic Surgery Using Ultrasound Scan to Measure Facial Swelling Vikram Shetty, MBBS, DNB, MDS,* and Amit Mohan, MDSy Purpose:
To evaluate the effectiveness of systemic enzyme therapy for the control of edema in patients who undergo bimaxillary orthognathic surgery.
Materials and Methods:
Thirty patients were included in this double-blinded, randomized, control trial. Before surgery, each patient was allotted a code (study or control group). Nine anthropometric points were selected. Thickness of the soft tissue at each of these points was measured using an ultrasound device. These measurements were performed on the day before surgery and 1, 5, and 15 days after surgery. The study group was given a twice-daily dose of systemic enzyme therapy from the first postoperative day for 5 days; the control group was given placebo. The percentage of difference in the thickness of the soft tissue was calculated at each of the 9 points on postoperative days 1, 5, and 15. These data were analyzed and compared using the Mann-Whitney test.
Results:
The statistical evaluation showed a significant difference in soft tissue thickness between the 2 groups, especially on days 5 and 15, at most assessed points.
Conclusion:
The results of this study suggest that systemic enzyme therapy significantly decreases postoperative edema in orthognathic surgery, precluding long-term corticosteroid use. Ó 2013 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg -:e1-e7, 2013
Orthognathic surgery requires reflection of the mucoperiosteum with bony osteotomy that leads to varying degrees of postoperative swelling. The presence of extensive swelling can compromise the airway, patient recovery, and surgical outcome.1 Several methods have been developed to measure facial soft tissue thickness in cadavers and in live patients.2 Traditionally, facial soft tissue measurements
have been studied using the needle depth probing method on cadavers.3 Several imaging-based methods for measuring living facial soft-tissue thickness have been reported.4 These include lateral cephalometric radiography,5 computed tomography,4,6 ultrasound,7 magnetic resonance imaging,8 and cone beam computed tomography.9 In the present study, ultrasound was used to assess facial soft-tissue thickness because of its reliability, easy availability, and patient safety. In maxillofacial surgery, various methods are used to decrease postoperative swelling, including pressure dressings, ice packs, and placement of drains. Another reported method to decrease postoperative edema in orthognathic surgery is using the endoscopic approach for ramus osteotomy.10 Medical management of swelling in orthognathic surgery is confined mainly to the use of steroids or nonsteroidal antiinflammatory drugs. The use of systemic enzyme therapy (SET) for edema control in orthognathic surgery is not well established in the literature.
Received from the Nitte Meenakshi Institute of Craniofacial Surgery, K.S. Hegde Hospital, Nitte University, Mangalore, Karnataka, India. *Director. ySurgical Fellow. Address correspondence and reprint requests to Dr Shetty: Nitte Meenakshi Institute of Craniofacial Surgery, K.S. Hegde Hospital, Nitte University, Mangalore, Karnataka, India 575018; e-mail: [email protected] Ó 2013 American Association of Oral and Maxillofacial Surgeons 0278-2391/13/00052-9$36.00/0 http://dx.doi.org/10.1016/j.joms.2013.01.008
e1
e2 The dispersible enzyme tablet contains a dispersible combination of trypsin (96 mg), bromelain (180 mg), and rutoside trihydrate (200 mg). This combination has antioxidant, anti-inflammatory, antiedematous, analgesic, antithrombotic, antiplatelet, and immunemodulating properties.
Mechanism of the Action of Enzymes The dispersible enzyme tablet is a combination of systemic cysteine and serine proteases. Trypsin is a serine endoproteinase that breaks peptide bonds inside protein molecules. Trypsin cleaves peptide chains mainly at the carboxyl side of the amino acid lysine or arginine except when either is followed by proline.11 Trypsin acts as a thrombolytic and fibrinolytic agent, thus cleaving the fibrin mantle and ensuring proper blood flow during wound healing. Bromelain is an unusually complex mixture of different thiol-endopeptidases and another, not yet completely characterized component, such as phosphatase. Bromelain contains various protease inhibitors. It converts plasminogen into plasmin, exerting mild antiinflammatory and antiedematous effects. It does not allow further release of arachidonic acid from cell membranes, having a favorable effect on prostaglandin synthesis.11 Rutoside trihydrate (rutin) is the rutinose glycoside form of quercetin. Rutin increases the strength of the walls of the blood capillaries and regulates their permeability to normalize pathologically increased vessel permeability. It also has antioxidant activity and antiinflammatory, antihistaminic, and antiviral properties.12 The purpose of this study was to evaluate the effectiveness of SET for the control of edema, using ultrasound for measuring soft-tissue thickness, in patients who underwent bimaxillary orthognathic surgery.
EDEMA CONTROL IN ORTHOGNATHIC SURGERY
Table 1. DESCRIPTION OF LANDMARK LOCATIONS ON THE FACE
p1
Mid-philtral
Centered between the nose and mouth on the midline p2 Mental eminence Centered on the forward-most projecting point of the chin on the midline p3 Mid-submental Centered between the lowermost point on the chin and neck on the midline p4r and p4l Gonion, right At angle of the mandible and left p5r and p5l Mid-mandibular, Centered between the right and left gonion and mental eminence 1 cm above the lower border of the mandible p6r and p6l Submandibular, Centered between the right and left gonion and mental eminence 1 cm below the lower border of the mandible Shetty and Mohan. Edema Control in Orthognathic Surgery. J Oral Maxillofac Surg 2013.
6 points (p4r and p4l, p5r and p5l, and p6r and p6l) located bilaterally. The selection of these landmarks was based on their presence in other studies and on the ability to reliably locate these landmarks in a standardized way on the faces of the volunteers.13 An additional requirement was that these points were not subject to change after bone repositioning during orthognathic surgery.
Materials and Methods SELECTION OF PATIENTS
In this double-blinded, randomized, control trial, 30 consecutive, medically fit individuals were included for whom bimaxillary orthognathic surgery (Le Fort I osteotomy plus bilateral sagittal split osteotomy plus genioplasty) was indicated. Before surgery, each patient was allotted a code (study or control group) based on a random number table by a single office assistant. The patients, surgical team, and ultrasonologist supervising the measurements were unaware of the code allotted. This study was approved by the Nitte University institutional review board, and all participants signed an informed consent agreement. SELECTION OF LANDMARKS
Nine anthropometric points were selected (Table 1, Figs 1, 2): 3 points (p1, p2, and p3) on the midline and
FIGURE 1. Photograph showing points marked on the face (frontal view). Shetty and Mohan. Edema Control in Orthognathic Surgery. J Oral Maxillofac Surg 2013.
e3
SHETTY AND MOHAN
in all patients 30 minutes before surgery. A similar dose of steroid was repeated once postoperatively. No surgical drains were placed and no ice packs were given to any patient. In addition to these measures, the study group was given a twice-daily dose of SET from the first postoperative day for 5 days by the office assistant who had initially allotted the codes to the patients; the control group was given placebo. The percentage of difference in soft tissue thickness was calculated at each of the 9 points on postoperative days 1, 5, and 15. These data were analyzed and compared using the Mann-Whitney test. FIGURE 2. Photograph showing points marked on the face (lateral view). Shetty and Mohan. Edema Control in Orthognathic Surgery. J Oral Maxillofac Surg 2013.
METHOD OF MEASUREMENT
The patients were asked to sit upright with a straight-head position. Soft-tissue thickness at each point was measured using an ultrasound device with a linear transducer of 7 to 14 MHz, minimal gel, and no pressure on the tissues, thus preventing tissue distortion. The thickness at points 1, 2, 4, and 5 was measured from the skin surface to the cortical bone. The thickness at point 3 was measured from the skin to the mylohyoid muscle and that at point 6 was measured from the skin to the submandibular gland. These measurements were performed on the day before surgery and postoperatively on days 1, 5, and 15. All measurements were recorded by a single operator (A.M.) and supervised by a single sonologist. All patients underwent Le Fort I osteotomy, bilateral sagittal split osteotomy, and genioplasty. All surgeries were performed under standardized operating conditions by the same surgeon (V.S.). The duration of surgery and the cheek retraction time were recorded for all patients. As a part of the routine premedication protocol, 1 dose of dexamethasone 8 mg was injected
Results Thirty patients were included in the study (n = 15 per group). The study group consisted of 9 men and 6 women, and the control group consisted of 7 men and 8 women. The mean age in the study group was 24.27 6.431 years and that in the control group was 24.93 6.734 years. The study and control groups were compared for intraoperative parameters, such as duration of surgery, tissue manipulation time, duration of anesthesia, and cheek retraction time. The mean duration of surgery for the study and control groups was approximately 2.5 to 3 hours. Statistical analysis of these parameters showed no significant difference between the 2 groups (Table 2). The change in soft-tissue thickness on postoperative days 1, 5, and 15 was compared between the study and control groups (Table 3, Fig 3). The statistical evaluation showed a significant difference between the 2 groups, especially on days 5 and 15, at most assessed points. In contrast, there was no significant difference found on days 5 and 15 at the upper lip point.
Discussion Some clinical trials have advocated the use of steroids for edema control in orthognathic surgery.14 This forms
Table 2. COMPARISON BETWEEN THE STUDY AND CONTROL GROUPS BASED ON VARIOUS PARAMETERS
Mean
Age (yr) Duration of manipulation (min.) Total duration of surgery (min.) Duration of anesthesia (min.) Duration of cheek retraction (min.)
SD
Study
Control
Study
Control
t Value
P Value
Interpretation
24.27 118.46 154.07 223.84 132.15
24.93 120.38 163.15 232.30 137.07
6.43 20.17 22.86 32.41 27.22
6.73 21.16 23.12 20.47 29.46
0.28 0.02 0.21 0.14 0.61
.784 .981 .837 .886 .546
NS NS NS NS NS
Abbreviations: NS, nonsignificant; SD, standard deviation; min., minute. Shetty and Mohan. Edema Control in Orthognathic Surgery. J Oral Maxillofac Surg 2013.
e4
EDEMA CONTROL IN ORTHOGNATHIC SURGERY
Table 3. STATISTICAL COMPARISON BETWEEN THE STUDY AND CONTROL GROUPS
Mean Landmarks p1
p2
p3
p4l
p4r
p5l
p5r
p6l
p6r
SD
Postoperative Day
Study
Control
Study
Control
Mann-Whitney Test (Z Value)
P Value
Interpretation
1 5 15 1 5 15 1 5 15 1 5 15 1 5 15 1 5 15 1 5 15 1 5 15 1 5 15
13.64 34.30 25.49 33.61 43.09 5.33 20.60 17.88 14.43 58.51 34.25 15.26 63.22 39.46 16.71 84.87 81.69 28.76 92.30 62.42 26.14 41.46 31.91 3.01 47.65 29.29 3.48
43.86 32.29 31.65 146.38 133.00 60.59 45.14 35.88 15.95 104.64 79.82 52.32 100.73 60.96 44.75 111.74 107.71 34.84 137.17 119.28 50.94 83.42 57.60 28.31 101.20 61.23 36.34
17.95 18.32 31.83 27.39 30.02 4.13 14.15 10.81 12.22 28.10 21.86 11.67 26.72 14.64 12.22 40.60 22.28 10.63 42.16 22.68 13.80 21.82 16.93 2.53 28.88 17.85 2.94
34.36 29.76 29.11 101.29 91.73 35.04 21.63 26.90 13.39 78.66 55.91 30.04 53.35 38.53 26.89 53.90 42.33 24.65 56.11 70.60 27.06 38.73 27.65 24.34 50.05 42.26 31.54
3.02 0.22 0.55 4.16 3.61 6.07 3.68 2.41 0.32 2.14 2.94 4.45 2.43 2.02 3.68 1.54 2.11 0.88 2.48 2.97 3.16 3.66 3.07 4.00 3.59 2.70 4.02
.001 .412 .290 .000 .000 .000 .000 .008 .373 .016 .002 .000 .007 .022 .000 .061 .018 .190 .007 .001 .001 .000 .001 .000 .000 .004 .000
S NS NS S S S S S NS S S S S S S NS S NS S S S S S S S S S
Abbreviations: NS, nonsignificant; S, significant; SD, standard deviation. Shetty and Mohan. Edema Control in Orthognathic Surgery. J Oral Maxillofac Surg 2013.
the basis for the use of an ‘ ultrashort’’ course (2 doses) of dexamethasone for edema control in the present patients. However, the authors’ clinical observation over a period longer than 5 years with the use of this steroid therapy for edema control in aesthetic procedures was not completely satisfactory. In contrast, a longer use of steroids is associated with multiple problems, such as skin changes, increased serum glucose, adrenal suppression, disturbed wound healing, and impaired immunity.1 This led the authors to test other alternatives with fewer side effects for use in aesthetic surgeries as an adjunct to the authors’ current ultrashort steroid therapy. Various nonmedical methods also have been used for edema control, each with limitations. The pressure dressing has limited application because of the complex anatomy of the maxillofacial region. Also, excessive pressure in the lower third of face and neck may cause severe discomfort and can compress the airway in some patients. The placement of extraoral drains in such aesthetic procedures is not justified because of
residual scar formation. Moreover, intraoral drains are not well tolerated by most patients. The use of ice bags to control edema after a maxillofacial procedure also has limited application.15 Various methods have been suggested in the literature to measure the amount of tissue edema. Methods for measuring and quantifying such a 3-dimensional phenomenon include 3-dimensional laser scanning and magnetic resonance imaging, but these are costly and not widely available.16,17 A simpler method is to measure at least 1 linear dimension of swelling under standardized conditions and to consider it representative of the entire swelling.18 However, this approach cannot be used in orthognathic surgery because such measurements can be altered as a result of bone repositioning during surgery. In the present study, ultrasonography was used to measure soft-tissue thickness. This method has been found to be simple, relatively inexpensive, accurate, and easily reproducible.13,19 Reliability for thickness
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SHETTY AND MOHAN
FIGURE 3. Bar graph showing percentage of increase in soft tissue thickness for the study and control groups on different postoperative days. Shetty and Mohan. Edema Control in Orthognathic Surgery. J Oral Maxillofac Surg 2013.
measurements is reasonably good and different anatomic structures are easily distinguishable to record the measurements.
There are various parameters that significantly influence the amount of soft-tissue swelling in orthognathic surgery. To decrease the influence of variables, such as
e6 type of surgery, extent of dissection, and duration of tissue manipulation, on the extent of swelling, these variables were standardized in the 2 groups. Hence, all patients included in the study were those who were indicated for Le Fort I osteotomy, bilateral sagittal split osteotomy, and genioplasty. All surgeries were performed by the same surgeon (V.S.) under similar surgical and anesthesia conditions such that the technique, time, and tissue manipulation during surgeries were standardized. Also, all patients were mobilized to a sitting position within 6 hours and were ambulatory within 24 hours. The soft-tissue thickness of the face varies among individuals. To standardize this parameter, the authors measured the soft tissue thickness preoperatively at various points and measured the percentage of change in thickness of the corresponding points at various postoperative intervals. All patients in the 2 groups received 2 doses of corticosteroids. In addition, patients in the study group received a 5-day course of SET. In this study, the authors noted a significant difference in soft-tissue thickness between the 2 groups. Thus, a direct correlation was observed between the use of SET and the decrease in postoperative swelling. In the present series of data, there was not much change in soft-tissue swelling observed in the midfacial region compared with the lower face. This can be explained by the belief that edema is greater in the mandibular region after orthognathic surgery.20 Hence, the effect of the drug is more significant in the lower facial region. SET uses specific enzyme compounds to increase enzyme levels throughout the body and improve the function of the various body systems primarily by modulating, controlling, and balancing the inflammatory and oxidative processes that occur throughout the various body systems. These enzymes work on balancing the immune system. These enzymes bind with a2-macroglobulin and activate it. This activated a2-macroglobulin acts like a magnet to all unwanted and excessive mediators of inflammation and attracts them to form a complex. This complex is cleared by the abundance of macrophages in the liver. The use of SET in the treatment and prevention of swelling in long bone trauma has been documented in the literature21; however, there are no clinical trials that suggest the possible benefit of such therapy in maxillofacial surgeries, in particular orthognathic surgery. The other documented indications for the combination include osteoarthritis,22 Alzheimer disease,23 and hepatitis.24 These enzymes are usually well tolerated by patients. However, some patients may complain of odorless and colorless stool, a sensation of fullness,
EDEMA CONTROL IN ORTHOGNATHIC SURGERY
flatulence, and occasional episodes of nausea with much higher dosages. These complaints were not noted in the present group of patients. The present study suggests that SET significantly decreases postoperative edema in orthognathic surgery, thus precluding long-term corticosteroid use.
References 1. Cheginia S, Dhariwal DK: Review of evidence for the use of steroids in orthognathic surgery. Br J Oral Maxillofac Surg 50: 97, 2012 2. Sahni D, Singh SG, Jit I, et al: Facial soft tissue thickness in Northwest Indian adults. Forensic Sci Int 179:137, 2008 3. Suazo GIC, Cantın LM, Zavando MDA, et al: Comparisons in soft-tissue thicknesses on the human face in fresh and embalmed corpses using needle puncture method. Int J Morphol 26:165, 2008 4. Kim DK, Ruprecht A, Wang G, et al: Accuracy of facial soft tissue thickness measurements in personal computer-based multiplanar reconstructed computed tomography images. Forensic Sci Int 155:28, 2005 5. George RM: The lateral craniographic method of facial reconstruction. J Forensic Sci 32:1305, 1987 6. Phillips VM, Smuts NA: Facial reconstruction: Utilization of computerized tomography to measure facial tissue thickness in a mixed racial population. Forensic Sci Int 83:51, 1996 7. El-Mehallawi IH, Soliman EM: Ultrasonic assessment of facial soft tissue thicknesses in adult Egyptians. Forensic Sci Int 117:99, 2001 8. Lam EW, Hannam AG, Wood WW, et al: Imaging orofacial tissues by magnetic resonance. Oral Surg Oral Pathol Oral Radiol Endod 68:2, 1989 9. Fourie Z, Damstra J, Gerrits PO, et al: Accuracy and reliability of facial soft tissue depth measurements using cone beam computer tomography. Forensic Sci Int 199:9, 2010 10. Williams WB, Abukawa H, Shuster V, et al: A comparison of postoperative edema after intraoral vs. endoscopic mandibular ramus osteotomy. J Oral Maxillofac Surg 61(8 suppl.):61a, 2003 11. Chang A, Scheer M, Grote A, et al: BRENDA, AMENDA and FRENDA the enzyme information system: New content and tools in 2009. Nucleic Acids Res 37:D588, 2009 12. Couch JF, Naghski J, Krewson CF: Rutin content of Sophora japonica L. J Am Chem Soc 74:424, 1952 13. Greef SD, Claes P, Mollemans W, et al: Semi-automated ultrasound facial soft tissue depth registration: Method and validation. J Forensic Sci 50:1, 2005 14. Weber CR, Griffin JM: Evaluation of dexamethasone for reducing postoperative oedema and inflammatory response after orthognathic surgery. J Oral Maxillofac Surg 52:35, 1994 15. Nusair YM: Local application of ice bags did not affect postoperative facial swelling after oral surgery in rabbits. Br J Oral Maxillofac Surg 45:48, 2007 16. Harrison JA, Nixon MA, Fright WR, Snape L: Use of hand-held laser scanning in the assessment of facial swelling: A preliminary study. Br J Oral Maxillofac Surg 42:8, 2004 17. Llewelyn J, Ryan M, Santosh C: The use of magnetic resonance imaging to assess swelling after the removal of third molar teeth. Br J Oral Maxillofac Surg 34:419, 1996 18. Laureano F, Filho JR, de Oliveira e Silva ED, et al: The influence of cryotherapy on reduction of swelling, pain and trismus after third-molar extraction: A preliminary study. J Am Dent Assoc 136:774, 2005 19. Kiliaridis S, K€alebo P: Masseter muscle thickness measured by ultrasonography and its relation to facial morphology. J Dent Res 70:1262, 1991 20. Anne EB, Torben HT, Else MP: Corticosteroid administration in oral and orthognathic surgery: A systematic review of the literature and meta-analysis. J Oral Maxillofac Surg 68:2207, 2010
SHETTY AND MOHAN 21. Kamenıcek V, Holan P, Franek P. [Systemic enzyme therapy in the treatment and prevention of post-traumatic and postoperative swelling]. Acta Chir Orthop Traumatol Cech 68:45, 2001 (in Czech) 22. Akhtar NM, Naseer R, Farooqi AZ, et al: Oral enzyme combination versus diclofenac in the treatment of osteoarthritis of the knee—A double-blind prospective randomized study. Clin Rheumatol 23:410, 2004
e7 23. Lauer D, Reichenbach A, Birkenmeier G: Alpha 2-macroglobulin-mediated degradation of amyloid beta 1-42: A mechanism to enhance amyloid beta catabolism. Exp Neurol 167: 385, 2001 24. Korpan MI, Korpan NN, Tschekman IS, et al. [Mechanism of therapeutic efficacy of Wobenzym in the treatment of toxic hepatitis. National Medical University, Kiev]. Dopovidi Nac Akad Nauk Ukrainy 9:184, 1997 (in Ukrainian)
A Prospective, Randomized, Double-Blind, Placebo-Controlled Clinical Trial Comparing the Efficacy of Systemic Enzyme Therapy for Edema Control in Orthognathic Surgery Using Ultrasound Scan to Measure Facial Swelling Vikram Shetty, MBBS, DNB, MDS,* and Amit Mohan, MDSy Purpose:
To evaluate the effectiveness of systemic enzyme therapy for the control of edema in patients who undergo bimaxillary orthognathic surgery.
Materials and Methods:
Thirty patients were included in this double-blinded, randomized, control trial. Before surgery, each patient was allotted a code (study or control group). Nine anthropometric points were selected. Thickness of the soft tissue at each of these points was measured using an ultrasound device. These measurements were performed on the day before surgery and 1, 5, and 15 days after surgery. The study group was given a twice-daily dose of systemic enzyme therapy from the first postoperative day for 5 days; the control group was given placebo. The percentage of difference in the thickness of the soft tissue was calculated at each of the 9 points on postoperative days 1, 5, and 15. These data were analyzed and compared using the Mann-Whitney test.
Results:
The statistical evaluation showed a significant difference in soft tissue thickness between the 2 groups, especially on days 5 and 15, at most assessed points.
Conclusion:
The results of this study suggest that systemic enzyme therapy significantly decreases postoperative edema in orthognathic surgery, precluding long-term corticosteroid use. Ó 2013 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg -:e1-e7, 2013
Orthognathic surgery requires reflection of the mucoperiosteum with bony osteotomy that leads to varying degrees of postoperative swelling. The presence of extensive swelling can compromise the airway, patient recovery, and surgical outcome.1 Several methods have been developed to measure facial soft tissue thickness in cadavers and in live patients.2 Traditionally, facial soft tissue measurements
have been studied using the needle depth probing method on cadavers.3 Several imaging-based methods for measuring living facial soft-tissue thickness have been reported.4 These include lateral cephalometric radiography,5 computed tomography,4,6 ultrasound,7 magnetic resonance imaging,8 and cone beam computed tomography.9 In the present study, ultrasound was used to assess facial soft-tissue thickness because of its reliability, easy availability, and patient safety. In maxillofacial surgery, various methods are used to decrease postoperative swelling, including pressure dressings, ice packs, and placement of drains. Another reported method to decrease postoperative edema in orthognathic surgery is using the endoscopic approach for ramus osteotomy.10 Medical management of swelling in orthognathic surgery is confined mainly to the use of steroids or nonsteroidal antiinflammatory drugs. The use of systemic enzyme therapy (SET) for edema control in orthognathic surgery is not well established in the literature.
Received from the Nitte Meenakshi Institute of Craniofacial Surgery, K.S. Hegde Hospital, Nitte University, Mangalore, Karnataka, India. *Director. ySurgical Fellow. Address correspondence and reprint requests to Dr Shetty: Nitte Meenakshi Institute of Craniofacial Surgery, K.S. Hegde Hospital, Nitte University, Mangalore, Karnataka, India 575018; e-mail: [email protected] Ó 2013 American Association of Oral and Maxillofacial Surgeons 0278-2391/13/00052-9$36.00/0 http://dx.doi.org/10.1016/j.joms.2013.01.008
e1
e2 The dispersible enzyme tablet contains a dispersible combination of trypsin (96 mg), bromelain (180 mg), and rutoside trihydrate (200 mg). This combination has antioxidant, anti-inflammatory, antiedematous, analgesic, antithrombotic, antiplatelet, and immunemodulating properties.
Mechanism of the Action of Enzymes The dispersible enzyme tablet is a combination of systemic cysteine and serine proteases. Trypsin is a serine endoproteinase that breaks peptide bonds inside protein molecules. Trypsin cleaves peptide chains mainly at the carboxyl side of the amino acid lysine or arginine except when either is followed by proline.11 Trypsin acts as a thrombolytic and fibrinolytic agent, thus cleaving the fibrin mantle and ensuring proper blood flow during wound healing. Bromelain is an unusually complex mixture of different thiol-endopeptidases and another, not yet completely characterized component, such as phosphatase. Bromelain contains various protease inhibitors. It converts plasminogen into plasmin, exerting mild antiinflammatory and antiedematous effects. It does not allow further release of arachidonic acid from cell membranes, having a favorable effect on prostaglandin synthesis.11 Rutoside trihydrate (rutin) is the rutinose glycoside form of quercetin. Rutin increases the strength of the walls of the blood capillaries and regulates their permeability to normalize pathologically increased vessel permeability. It also has antioxidant activity and antiinflammatory, antihistaminic, and antiviral properties.12 The purpose of this study was to evaluate the effectiveness of SET for the control of edema, using ultrasound for measuring soft-tissue thickness, in patients who underwent bimaxillary orthognathic surgery.
EDEMA CONTROL IN ORTHOGNATHIC SURGERY
Table 1. DESCRIPTION OF LANDMARK LOCATIONS ON THE FACE
p1
Mid-philtral
Centered between the nose and mouth on the midline p2 Mental eminence Centered on the forward-most projecting point of the chin on the midline p3 Mid-submental Centered between the lowermost point on the chin and neck on the midline p4r and p4l Gonion, right At angle of the mandible and left p5r and p5l Mid-mandibular, Centered between the right and left gonion and mental eminence 1 cm above the lower border of the mandible p6r and p6l Submandibular, Centered between the right and left gonion and mental eminence 1 cm below the lower border of the mandible Shetty and Mohan. Edema Control in Orthognathic Surgery. J Oral Maxillofac Surg 2013.
6 points (p4r and p4l, p5r and p5l, and p6r and p6l) located bilaterally. The selection of these landmarks was based on their presence in other studies and on the ability to reliably locate these landmarks in a standardized way on the faces of the volunteers.13 An additional requirement was that these points were not subject to change after bone repositioning during orthognathic surgery.
Materials and Methods SELECTION OF PATIENTS
In this double-blinded, randomized, control trial, 30 consecutive, medically fit individuals were included for whom bimaxillary orthognathic surgery (Le Fort I osteotomy plus bilateral sagittal split osteotomy plus genioplasty) was indicated. Before surgery, each patient was allotted a code (study or control group) based on a random number table by a single office assistant. The patients, surgical team, and ultrasonologist supervising the measurements were unaware of the code allotted. This study was approved by the Nitte University institutional review board, and all participants signed an informed consent agreement. SELECTION OF LANDMARKS
Nine anthropometric points were selected (Table 1, Figs 1, 2): 3 points (p1, p2, and p3) on the midline and
FIGURE 1. Photograph showing points marked on the face (frontal view). Shetty and Mohan. Edema Control in Orthognathic Surgery. J Oral Maxillofac Surg 2013.
e3
SHETTY AND MOHAN
in all patients 30 minutes before surgery. A similar dose of steroid was repeated once postoperatively. No surgical drains were placed and no ice packs were given to any patient. In addition to these measures, the study group was given a twice-daily dose of SET from the first postoperative day for 5 days by the office assistant who had initially allotted the codes to the patients; the control group was given placebo. The percentage of difference in soft tissue thickness was calculated at each of the 9 points on postoperative days 1, 5, and 15. These data were analyzed and compared using the Mann-Whitney test. FIGURE 2. Photograph showing points marked on the face (lateral view). Shetty and Mohan. Edema Control in Orthognathic Surgery. J Oral Maxillofac Surg 2013.
METHOD OF MEASUREMENT
The patients were asked to sit upright with a straight-head position. Soft-tissue thickness at each point was measured using an ultrasound device with a linear transducer of 7 to 14 MHz, minimal gel, and no pressure on the tissues, thus preventing tissue distortion. The thickness at points 1, 2, 4, and 5 was measured from the skin surface to the cortical bone. The thickness at point 3 was measured from the skin to the mylohyoid muscle and that at point 6 was measured from the skin to the submandibular gland. These measurements were performed on the day before surgery and postoperatively on days 1, 5, and 15. All measurements were recorded by a single operator (A.M.) and supervised by a single sonologist. All patients underwent Le Fort I osteotomy, bilateral sagittal split osteotomy, and genioplasty. All surgeries were performed under standardized operating conditions by the same surgeon (V.S.). The duration of surgery and the cheek retraction time were recorded for all patients. As a part of the routine premedication protocol, 1 dose of dexamethasone 8 mg was injected
Results Thirty patients were included in the study (n = 15 per group). The study group consisted of 9 men and 6 women, and the control group consisted of 7 men and 8 women. The mean age in the study group was 24.27 6.431 years and that in the control group was 24.93 6.734 years. The study and control groups were compared for intraoperative parameters, such as duration of surgery, tissue manipulation time, duration of anesthesia, and cheek retraction time. The mean duration of surgery for the study and control groups was approximately 2.5 to 3 hours. Statistical analysis of these parameters showed no significant difference between the 2 groups (Table 2). The change in soft-tissue thickness on postoperative days 1, 5, and 15 was compared between the study and control groups (Table 3, Fig 3). The statistical evaluation showed a significant difference between the 2 groups, especially on days 5 and 15, at most assessed points. In contrast, there was no significant difference found on days 5 and 15 at the upper lip point.
Discussion Some clinical trials have advocated the use of steroids for edema control in orthognathic surgery.14 This forms
Table 2. COMPARISON BETWEEN THE STUDY AND CONTROL GROUPS BASED ON VARIOUS PARAMETERS
Mean
Age (yr) Duration of manipulation (min.) Total duration of surgery (min.) Duration of anesthesia (min.) Duration of cheek retraction (min.)
SD
Study
Control
Study
Control
t Value
P Value
Interpretation
24.27 118.46 154.07 223.84 132.15
24.93 120.38 163.15 232.30 137.07
6.43 20.17 22.86 32.41 27.22
6.73 21.16 23.12 20.47 29.46
0.28 0.02 0.21 0.14 0.61
.784 .981 .837 .886 .546
NS NS NS NS NS
Abbreviations: NS, nonsignificant; SD, standard deviation; min., minute. Shetty and Mohan. Edema Control in Orthognathic Surgery. J Oral Maxillofac Surg 2013.
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EDEMA CONTROL IN ORTHOGNATHIC SURGERY
Table 3. STATISTICAL COMPARISON BETWEEN THE STUDY AND CONTROL GROUPS
Mean Landmarks p1
p2
p3
p4l
p4r
p5l
p5r
p6l
p6r
SD
Postoperative Day
Study
Control
Study
Control
Mann-Whitney Test (Z Value)
P Value
Interpretation
1 5 15 1 5 15 1 5 15 1 5 15 1 5 15 1 5 15 1 5 15 1 5 15 1 5 15
13.64 34.30 25.49 33.61 43.09 5.33 20.60 17.88 14.43 58.51 34.25 15.26 63.22 39.46 16.71 84.87 81.69 28.76 92.30 62.42 26.14 41.46 31.91 3.01 47.65 29.29 3.48
43.86 32.29 31.65 146.38 133.00 60.59 45.14 35.88 15.95 104.64 79.82 52.32 100.73 60.96 44.75 111.74 107.71 34.84 137.17 119.28 50.94 83.42 57.60 28.31 101.20 61.23 36.34
17.95 18.32 31.83 27.39 30.02 4.13 14.15 10.81 12.22 28.10 21.86 11.67 26.72 14.64 12.22 40.60 22.28 10.63 42.16 22.68 13.80 21.82 16.93 2.53 28.88 17.85 2.94
34.36 29.76 29.11 101.29 91.73 35.04 21.63 26.90 13.39 78.66 55.91 30.04 53.35 38.53 26.89 53.90 42.33 24.65 56.11 70.60 27.06 38.73 27.65 24.34 50.05 42.26 31.54
3.02 0.22 0.55 4.16 3.61 6.07 3.68 2.41 0.32 2.14 2.94 4.45 2.43 2.02 3.68 1.54 2.11 0.88 2.48 2.97 3.16 3.66 3.07 4.00 3.59 2.70 4.02
.001 .412 .290 .000 .000 .000 .000 .008 .373 .016 .002 .000 .007 .022 .000 .061 .018 .190 .007 .001 .001 .000 .001 .000 .000 .004 .000
S NS NS S S S S S NS S S S S S S NS S NS S S S S S S S S S
Abbreviations: NS, nonsignificant; S, significant; SD, standard deviation. Shetty and Mohan. Edema Control in Orthognathic Surgery. J Oral Maxillofac Surg 2013.
the basis for the use of an ‘ ultrashort’’ course (2 doses) of dexamethasone for edema control in the present patients. However, the authors’ clinical observation over a period longer than 5 years with the use of this steroid therapy for edema control in aesthetic procedures was not completely satisfactory. In contrast, a longer use of steroids is associated with multiple problems, such as skin changes, increased serum glucose, adrenal suppression, disturbed wound healing, and impaired immunity.1 This led the authors to test other alternatives with fewer side effects for use in aesthetic surgeries as an adjunct to the authors’ current ultrashort steroid therapy. Various nonmedical methods also have been used for edema control, each with limitations. The pressure dressing has limited application because of the complex anatomy of the maxillofacial region. Also, excessive pressure in the lower third of face and neck may cause severe discomfort and can compress the airway in some patients. The placement of extraoral drains in such aesthetic procedures is not justified because of
residual scar formation. Moreover, intraoral drains are not well tolerated by most patients. The use of ice bags to control edema after a maxillofacial procedure also has limited application.15 Various methods have been suggested in the literature to measure the amount of tissue edema. Methods for measuring and quantifying such a 3-dimensional phenomenon include 3-dimensional laser scanning and magnetic resonance imaging, but these are costly and not widely available.16,17 A simpler method is to measure at least 1 linear dimension of swelling under standardized conditions and to consider it representative of the entire swelling.18 However, this approach cannot be used in orthognathic surgery because such measurements can be altered as a result of bone repositioning during surgery. In the present study, ultrasonography was used to measure soft-tissue thickness. This method has been found to be simple, relatively inexpensive, accurate, and easily reproducible.13,19 Reliability for thickness
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FIGURE 3. Bar graph showing percentage of increase in soft tissue thickness for the study and control groups on different postoperative days. Shetty and Mohan. Edema Control in Orthognathic Surgery. J Oral Maxillofac Surg 2013.
measurements is reasonably good and different anatomic structures are easily distinguishable to record the measurements.
There are various parameters that significantly influence the amount of soft-tissue swelling in orthognathic surgery. To decrease the influence of variables, such as
e6 type of surgery, extent of dissection, and duration of tissue manipulation, on the extent of swelling, these variables were standardized in the 2 groups. Hence, all patients included in the study were those who were indicated for Le Fort I osteotomy, bilateral sagittal split osteotomy, and genioplasty. All surgeries were performed by the same surgeon (V.S.) under similar surgical and anesthesia conditions such that the technique, time, and tissue manipulation during surgeries were standardized. Also, all patients were mobilized to a sitting position within 6 hours and were ambulatory within 24 hours. The soft-tissue thickness of the face varies among individuals. To standardize this parameter, the authors measured the soft tissue thickness preoperatively at various points and measured the percentage of change in thickness of the corresponding points at various postoperative intervals. All patients in the 2 groups received 2 doses of corticosteroids. In addition, patients in the study group received a 5-day course of SET. In this study, the authors noted a significant difference in soft-tissue thickness between the 2 groups. Thus, a direct correlation was observed between the use of SET and the decrease in postoperative swelling. In the present series of data, there was not much change in soft-tissue swelling observed in the midfacial region compared with the lower face. This can be explained by the belief that edema is greater in the mandibular region after orthognathic surgery.20 Hence, the effect of the drug is more significant in the lower facial region. SET uses specific enzyme compounds to increase enzyme levels throughout the body and improve the function of the various body systems primarily by modulating, controlling, and balancing the inflammatory and oxidative processes that occur throughout the various body systems. These enzymes work on balancing the immune system. These enzymes bind with a2-macroglobulin and activate it. This activated a2-macroglobulin acts like a magnet to all unwanted and excessive mediators of inflammation and attracts them to form a complex. This complex is cleared by the abundance of macrophages in the liver. The use of SET in the treatment and prevention of swelling in long bone trauma has been documented in the literature21; however, there are no clinical trials that suggest the possible benefit of such therapy in maxillofacial surgeries, in particular orthognathic surgery. The other documented indications for the combination include osteoarthritis,22 Alzheimer disease,23 and hepatitis.24 These enzymes are usually well tolerated by patients. However, some patients may complain of odorless and colorless stool, a sensation of fullness,
EDEMA CONTROL IN ORTHOGNATHIC SURGERY
flatulence, and occasional episodes of nausea with much higher dosages. These complaints were not noted in the present group of patients. The present study suggests that SET significantly decreases postoperative edema in orthognathic surgery, thus precluding long-term corticosteroid use.
References 1. Cheginia S, Dhariwal DK: Review of evidence for the use of steroids in orthognathic surgery. Br J Oral Maxillofac Surg 50: 97, 2012 2. Sahni D, Singh SG, Jit I, et al: Facial soft tissue thickness in Northwest Indian adults. Forensic Sci Int 179:137, 2008 3. Suazo GIC, Cantın LM, Zavando MDA, et al: Comparisons in soft-tissue thicknesses on the human face in fresh and embalmed corpses using needle puncture method. Int J Morphol 26:165, 2008 4. Kim DK, Ruprecht A, Wang G, et al: Accuracy of facial soft tissue thickness measurements in personal computer-based multiplanar reconstructed computed tomography images. Forensic Sci Int 155:28, 2005 5. George RM: The lateral craniographic method of facial reconstruction. J Forensic Sci 32:1305, 1987 6. Phillips VM, Smuts NA: Facial reconstruction: Utilization of computerized tomography to measure facial tissue thickness in a mixed racial population. Forensic Sci Int 83:51, 1996 7. El-Mehallawi IH, Soliman EM: Ultrasonic assessment of facial soft tissue thicknesses in adult Egyptians. Forensic Sci Int 117:99, 2001 8. Lam EW, Hannam AG, Wood WW, et al: Imaging orofacial tissues by magnetic resonance. Oral Surg Oral Pathol Oral Radiol Endod 68:2, 1989 9. Fourie Z, Damstra J, Gerrits PO, et al: Accuracy and reliability of facial soft tissue depth measurements using cone beam computer tomography. Forensic Sci Int 199:9, 2010 10. Williams WB, Abukawa H, Shuster V, et al: A comparison of postoperative edema after intraoral vs. endoscopic mandibular ramus osteotomy. J Oral Maxillofac Surg 61(8 suppl.):61a, 2003 11. Chang A, Scheer M, Grote A, et al: BRENDA, AMENDA and FRENDA the enzyme information system: New content and tools in 2009. Nucleic Acids Res 37:D588, 2009 12. Couch JF, Naghski J, Krewson CF: Rutin content of Sophora japonica L. J Am Chem Soc 74:424, 1952 13. Greef SD, Claes P, Mollemans W, et al: Semi-automated ultrasound facial soft tissue depth registration: Method and validation. J Forensic Sci 50:1, 2005 14. Weber CR, Griffin JM: Evaluation of dexamethasone for reducing postoperative oedema and inflammatory response after orthognathic surgery. J Oral Maxillofac Surg 52:35, 1994 15. Nusair YM: Local application of ice bags did not affect postoperative facial swelling after oral surgery in rabbits. Br J Oral Maxillofac Surg 45:48, 2007 16. Harrison JA, Nixon MA, Fright WR, Snape L: Use of hand-held laser scanning in the assessment of facial swelling: A preliminary study. Br J Oral Maxillofac Surg 42:8, 2004 17. Llewelyn J, Ryan M, Santosh C: The use of magnetic resonance imaging to assess swelling after the removal of third molar teeth. Br J Oral Maxillofac Surg 34:419, 1996 18. Laureano F, Filho JR, de Oliveira e Silva ED, et al: The influence of cryotherapy on reduction of swelling, pain and trismus after third-molar extraction: A preliminary study. J Am Dent Assoc 136:774, 2005 19. Kiliaridis S, K€alebo P: Masseter muscle thickness measured by ultrasonography and its relation to facial morphology. J Dent Res 70:1262, 1991 20. Anne EB, Torben HT, Else MP: Corticosteroid administration in oral and orthognathic surgery: A systematic review of the literature and meta-analysis. J Oral Maxillofac Surg 68:2207, 2010
SHETTY AND MOHAN 21. Kamenıcek V, Holan P, Franek P. [Systemic enzyme therapy in the treatment and prevention of post-traumatic and postoperative swelling]. Acta Chir Orthop Traumatol Cech 68:45, 2001 (in Czech) 22. Akhtar NM, Naseer R, Farooqi AZ, et al: Oral enzyme combination versus diclofenac in the treatment of osteoarthritis of the knee—A double-blind prospective randomized study. Clin Rheumatol 23:410, 2004
e7 23. Lauer D, Reichenbach A, Birkenmeier G: Alpha 2-macroglobulin-mediated degradation of amyloid beta 1-42: A mechanism to enhance amyloid beta catabolism. Exp Neurol 167: 385, 2001 24. Korpan MI, Korpan NN, Tschekman IS, et al. [Mechanism of therapeutic efficacy of Wobenzym in the treatment of toxic hepatitis. National Medical University, Kiev]. Dopovidi Nac Akad Nauk Ukrainy 9:184, 1997 (in Ukrainian)