Maxillary sinus floor augmentation for dental implantation is a well-established procedure for patients with extensive resorption of the posterior maxilla.1–6 Several investigators have successfully treated the maxillary sinus expansion via different techniques of sinus augmentation.7–9 The most commonly reported intraoperative complication with a lateral window approach to sinus elevation has been the perforation of the sinus membrane.10,11 This complication is noteworthy because excessively large perforations may necessitate the abortion of the procedure, cause a delay in treatment, or necessitate additional treatment associated with direct communication into the sinus.12,13
Marx and Garg14 described an easy method as an aid for elevation of the sinus membrane for the sinus augmentation procedure. They applied a cottonoid soaked with epinephrine in the maxillary sinus after the sinus membrane had been adequately reflected. They reported that it helped to create vasoconstriction and hemostasis but also were able to reflect the sinus membrane bluntly and gently with minimal risk of a membrane perforation.14
Topical vasoconstrictors are important hemostatic agents for maximizing visualization and minimizing bleeding during sinus surgeries. The major difficulty with the epinephrine is to establish the dose that provides the best safety and efficacy. However, these topical agents have the potential to elicit systemic cardiopulmonary effects, and currently there are no guidelines or established protocol that is available to aid the surgeon balancing the safety and efficacy.15,16 Therefore, the objective of this study was to evaluate the safety of epinephrine as a topical vasoconstrictor in sinus augmentation procedures.
Patients and Methods
Forty-three healthy, normotensive medication-free patients of both sexes with ages ranging from 29 to 72 years (47.1 ± 9.9 years), who require unilateral or bilateral sinus augmentation for dental implant placement, were enrolled in this study. Patients undergoing medical treatment for unstable angina, recent myocardial infarction or revascularization surgery, in refractory arrhythmias, arterial hypertension, and decompensated congestive heart failure were excluded from the study. The patients with other systemic conditions were included in the study. All patients were nonsmokers. The study was approved by the local ethics committee, and written informed consent was obtained from all patients before the operation.
Patients were divided into 2 groups according to the application of either epinephrine-soaked cottonoid or saline-soaked cottonoid. The patients were assigned to each group randomly. The study group consisted of 23 patients whose ages ranged from 29 to 72 years (46.9 ± 9.8 years), whereas the control group consisted of 20 patients whose ages ranged from 30–70 years (47.4 ± 10.3 years).
The surgical procedure was performed following the guidelines described by Marx and Garg.14 All operations were performed under local anesthesia. Preoperative sedation was not used in any patient. The anesthesia was carried out by regional posterior and middle superior alveolar branches and greater palatine nerve by 4 mL of 4% articaine with 1/100,000 epinephrine (Ultracain D-S Forte; Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany). After a full-thickness flap was elevated slightly palatal to the crest of the ridge, a lateral antrostomy was created by outlining an island of bone. The sinus membrane was adequately reflected. All membranes were intact at the time of reflection. Any complications like perforation or laceration of the sinus membrane was not observed. In group A, after the elevation of the membrane, a cottonoid (Arora Cotton Sponges 5 × 5 cm; Turkiz Medical, Adana, Turkey) soaked with 4 mL of 4% articaine with 1:100,000 epinephrine (Ultracain D-S Forte; Sanofi-Aventis Deutschland GmbH) was gently placed in the maxillary sinus; in group B, a cottonoid soaked with sterile saline was gently placed in the maxillary sinus; both were left in place for 10 minutes. The cottonoid was removed, and sufficient elevation of the sinus membrane for the graft material was confirmed. The graft material (Geistlich Bio-Oss; Geistlich Pharma AG, Switzerland) was placed under the sinus membrane into the recesses of the sinus floor. The lateral window and graft material were covered by a collagen membrane (Geistlich Bio-Gide; Geistlich Pharma AG), and the flap was secured using a braided nonabsorbable 3/0 silk suture (Dogsan Surgical Sutures, Istanbul, Turkey) with primary closure. If a bilateral sinus floor augmentation had to be done for the patient, only the data obtained from the first operated side were included in this study.
The arterial blood pressure and heart rate monitoring was carried out with a PETAŞ KMA 800 device (PETAŞ Professional Electronics Industry, Inc., Ankara, Turkey), attached to the patient by a standard cuff. The left arm of the patients were placed parallel to the body, and the arterial pressure measuring cuff was aligned with the heart so that the noninvasive pressure monitor would work in proper conditions. After the subject was prepared, the appliance was automatically calibrated by allowing it to record for 10 minutes, a sufficient length of time to stabilize parameters and determine a scale of values for systolic and diastolic arterial pressures, in mm Hg, and heart rate, in beats per minute, for each patient. These mean values were used as a control.
The operations were carried out with continuous monitoring of systolic and diastolic arterial pressure and heart rate from the time the subject was being prepared until 10 minutes after the end of the procedure. Cardiovascular parameters were assessed at the following stages: immediately after patient preparation for 10 minutes, before local anesthetic injection, immediately after anesthetic injection, 1 minute after epinephrine/saline-soaked cotton application, 5 minutes after epinephrine/saline-soaked cotton application, 10 minutes after epinephrine/saline-soaked cotton application, and finally after the end of the operation for 10 minutes.
The data obtained in the first 10 minutes before local anesthetic injection were used as control in relation to the measurements in the subsequent phases. The phases of the study are shown in Table 1.
A 100-mm flat-line visual analog scale (VAS) was used for evaluation of anxiety levels of the patients before the operation. Assuming that systemic hemodynamics might be affected by physiological epinephrine production as the response to the stress of the surgery or anxiety lead the authors to compare the anxiety levels of control and study groups. None of our patients declared that they experienced pain during the surgery; therefore, we ruled out the effect of physiological epinephrine production as the response to the pain on systemic hemodynamics.
The repeated-measures analysis of variance was applied to analyze the time-dependent changes in both groups. The Bonferroni multiple comparisons test (adjusted for repeated measures) was applied to identify the moments that differed. The chi-square test or Fisher exact test was used to compare qualitative variables among the groups. The significance level was set to be 5%. Independent t test was applied to compare anxiety between both groups. P value of less than 0.05 was considered to be statistically significant.
No arrhythmias or hypertensive peaks were detected in any patient during perioperative cardiocirculatory monitoring.
In the study group, 4 mL of 4% articaine, 1/100,000 epinephrine for regional anesthesia, and 4 mL of 4% articaine, 1/100,000 epinephrine for topical administration on the maxillary sinus membrane, were used. Therefore, the articaine and epinephrine dosages used for either anesthesia or administration was to the sinus membrane were 80 mg and 48 µg, respectively.
In the control group, 4 mL of 4% articaine, 1/100,000 epinephrine, for regional anesthesia was injected. On the contrary to the study group, sterile saline for topical administration to the maxillary sinus membrane were used in the control subject. The articaine and epinephrine dosages used for either anesthesia or administration to the sinus membrane were 40 mg and 24 µg, respectively.
Figure 1 shows that the highest variations of systolic blood pressure in the study group occurred at the phases of 1 minute after epinephrine-soaked cotton application (3.8%) and 5 minutes after epinephrine-soaked cotton application (3.4%) (P > 0.05). In the control group, the highest variations of systolic blood pressure occurred at the phases of immediately after anesthesia (4.8%) and before anesthesia (4%) (P > 0.05).
Figure 2 shows the greatest changes in diastolic blood pressure in the study group occurred at the phases of 1 minute after epinephrine-soaked cotton application (5.9%) and 5 minutes after epinephrine-soaked cotton application (5.0%) (P > 0.05). In the control group, the greatest changes in diastolic blood pressure occurred at the phases of immediately after anesthesia (5.3%) and 1 minute after saline-soaked cotton application (5.2%) (P > 0.05). Although, there was an increase in both study and control groups, no statistical significance was observed in either systolic or diastolic blood pressure.
Figure 3 shows that the highest heart rate variations in the study group were 5.4% and 4.6% at the phases of 1 minute and 5 minutes after epinephrine-soaked cotton application, respectively. In the control group, the highest heart rate variations were 6.5% and 5% at the phases immediately after anesthesia and before anesthesia, respectively (P > 0.05). Although there were no significant changes according to statistical analysis in both groups (P > 0.05), mean changes of cardiocirculatory values along the operation in both groups are shown in Table 2. The comparison of systolic blood pressure, diastolic blood pressure, and heart rate among the study and control groups indicated an absence of alterations in these variables related to whether epinephrine- or saline-soaked cottonoid used for maxillary sinus floor augmentation (P > 0.05).
Mean anxiety VAS scores for study and control groups were 31.1 ± 14.00 and 29.8 ± 14.27, respectively. However, the difference in VAS scores for anxiety was found to be statistically insignificant among groups (P > 0.05).
Epinephrine is one of the most commonly used vasoconstrictors in association with local anesthesia in dentistry, indisputably the most studied.17–19 Its use in dentistry, as well as that of other vasoconstrictors, is widely accepted. Reports in the literature for epinephrine concentrations for topical use vary widely ranging from 1:200,000 to 1:1000 for topical use.16,17,20–26 Systemic side effects are dependent upon the absorption of epinephrine. The efficacy of epinephrine may be further affected by its method of application. The adverse effects of epinephrine can be summarized as tachycardia, hypertension, palpitation, arrhythmia, and anxiety. Epinephrine can cause excessive vasoconstriction causing peripheral gangrene, impaired organ perfusion, increased overload, and cardiovascular collapse at high doses; however, the occurrence of most adverse reactions is due to inappropriate high-dose injections or accidental intravascular punctures.16,27–29
Epinephrine application on the sinus membrane is considered an effective method by contracting the capillary vessels in the sinus mucosa to avoid bleeding. However, the application of epinephrine presents a risk for hypertension or tachycardia that can be induced by the absorption of topically applied epinephrine to the systemic circulation. The maxillary vascular network is particularly extensive guaranteeing a high amount of blood flow. Complex vascularization of the maxillary sinus mainly composed of the posterior superior alveolar artery (also known as alveolar antral artery), infraorbital artery, small branches of the posterior lateral nasal arteries, and some anastomoses between the descending palatine artery and sphenopalatine artery.30 The venous system is collected either by a single trunk, which is a continuation of the sphenopalatine vein, or by 3 venous plexuses: the anterior and posterior pterygoid plexuses, and the alveolar plexus.31 Because of this complex vascular network, absorption and appearance of systemic effects of topically applied epinephrine were considered to be fast and distinctive.
Since the publication of Marx and Garg,14 introducing the use of epinephrine for sinus augmentation procedures, the systemic effects of the technique have not been investigated yet. Thus, in our study, we aimed to evaluate the safety of epinephrine as a topical agent in sinus augmentation procedures. However, there were no significant changes either in heart rate or in systolic and diastolic blood pressures.
In a prospective study, Kameyama et al28 investigated the influences of nasal pretreatment with a mixed solution of epinephrine and lidocaine on the systemic hemodynamics and reported that the serum concentration of epinephrine in the systemic circulation significantly increased after absorption of topical epinephrine through the nasal mucosa; however, there were no differences in the systemic hemodynamics after application of topical epinephrine.28 In our study, we did not intend to investigate serum concentration changes of epinephrine in the systemic circulation, but similar to the study by Kameyama et al28, we found that there were no differences in the systemic hemodynamics after application of topical epinephrine through sinus membrane.
Adequate pain control is essential during oral surgical procedures. The oral cavity is densely filled with pain-triggering structures. Substances that provide more profound anesthesia are necessary to prevent stress.32 Epinephrine is not a synthetic substance; it is produced by the adrenal gland, which may increase its production in response to stressful conditions, including the stress of surgery and anxiety.16 It may rise and fall along the different stages of the operations due to the anxiety or pain that the patients were experiencing. Fortunately, none of our patients declared that they experienced pain during the surgery in our study. The data obtained from all patients in the first 10 minutes before the procedure were used as a control to compare the parameters in subsequent phases, and VAS scoring was used for evaluation of anxiety levels of the patients before the operation to rule out the physiological epinephrine production as the response to the anxiety effecting the results among groups.
A lateral approach for augmentation of the maxillary sinus floor can safely and predictably increase the vertical bone height for implant placement in patients with hyperpneumatized sinus.14 The most frequently occurring complication is perforation of the sinus membrane, which is reported in from 10% to 60% of cases.33–35 Once the sinus membrane is accessed, it must be carefully elevated to a level equal to or greater than the superior aspect of the lateral antrostomy.36 Hand instruments such as curettes are used to separate the sinus membrane from the walls of the maxillary sinus with traditional techniques.37 This is a delicate procedure that occasionally results in membrane perforation. Sinus membrane perforation may cause additional complications by itself such as increased risk of infection, abortion of the procedure, delay in treatment, or additional cost to repair the perforated sinus membrane.10–13 With regard to our clinical experience on this procedure, we can clearly confirm that use of epinephrine either enhances the visibility and correspondingly the safety of the procedure by creating vasoconstriction and hemostasis or simplifies elevation by helping the sinus membrane shrink itself, providing further reflection of the sinus membrane bluntly and gently with the minimal risk of membrane perforation.
The idea that higher concentrations of epinephrine were needed for improved visibility and operability in the procedures that may have a risk of bleeding has gained strength recently.15,16 Although the trend was to use more concentrated solutions, studies reporting on improved hemostasis and safety with these concentrations are still lacking. Systemic adverse effects are dependent on the absorption of epinephrine by the site of admission, which is another topic that has been poorly investigated.
In this study, we applied 1/100,000 epinephrine as a topical agent as Marx and Garg14 reported in the literature to evaluate efficacy and safety. In our opinion, topical application of 1/100,000 concentration of epinephrine ensures efficacy by creating vasoconstriction and hemostasis and helping to elevate the sinus membrane bluntly and gently. Topical application of 1/100,000 concentration of epinephrine also enables the changes in systemic hemodynamics to be within safe limitations. Although increasing the epinephrine concentration may enhance the efficacy, the risk of systemic adverse effects increase as well.
The literature recommends that the use of adrenergic vasoconstrictors should be avoided in patients with unstable angina, recent myocardial infarction or revascularization surgery, in refractory arrhythmias, noncontrolled arterial hypertension, and decompensated congestive heart failure.38 The patients included in this study were healthy, normotensive, and medication-free individuals. Therefore, our study does not represent a population that reflects the reality of oral and maxillofacial surgical practice so it may not be safe to perform this procedure in patients with cardiovascular problems. Studies focusing on the safety of using topical epinephrine admission for sinus floor augmentation in patients with cardiovascular diseases would be beneficial for additional oral and maxillofacial surgical practice because the patients who seek this procedure were mostly elderly individuals with cardiovascular problems.
In conclusion, the use of 4% articaine with epinephrine 1/100,000 for sinus floor augmentation resulted in statistically no changes in cardiocirculatory parameters like heart rate, systolic, and diastolic blood pressures in healthy individuals; however, additional studies are required.
The authors claim to have no financial interest, either directly or indirectly, in the products or information listed in the article.
1. Manor Y, Mardinger O, Bietlitum I, et al.. Late signs and symptoms of maxillary sinusitis after sinus augmentation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;110:e1–e4.
2. Lundgren S, Andersson S, Gualini F, et al.. Bone reformation with sinus membrane elevation: A new surgical technique for maxillary sinus floor augmentation
. Clin Implant Dent Relat Res. 2004;6:165–173.
3. Chen TW, Chang HS, Leung KW, et al.. Implant placement immediately after the lateral approach of the trap door window procedure to create a maxillary sinus lift without bone grafting: A 2-year retrospective evaluation of 47 implants in 33 patients. J Oral Maxillofac Surg. 2007;65:2324–2328.
4. Esposito M, Grusovin MG, Rees J, et al.. Effectiveness of sinus lift procedures for dental implant rehabilitation: A Cochrane systematic review. Eur J Oral Implantol. 2010;3:7–26.
5. Kahnberg KE, Ekestubbe A, Grondahl K, et al.. Sinus lifting procedure. I. One-stage surgery with bone transplant and implants. Clin Oral Implants Res. 2001;12:479–487.
6. Del Fabbro M, Testori T, Francetti L, et al.. Systematic review of survival rates for implants placed in the grafted maxillary sinus. Int J Periodontics Restorative Dent. 2004;24:565–577.
7. Tatum H Jr. Maxillary and sinus implant reconstructions. Dent Clin North Am. 1986;30:207–229.
8. Boyne PJ, James RA. Grafting of the maxillary sinus floor with autogenous marrow and bone. J Oral Surg. 1980;38:613–616.
9. Sailer H. The principle of removal of the sinus floor mucosa for new preprosthetic reconstruction methods (sinus inlay methods). In: Fonseca R, Davies WH, eds. Reconstructive Preprosthetic Oral and Maxillofacial Surgery. 2nd ed. Philadelphia, PA: Saunders. 1995:457–464.
10. Barone A, Santini S, Sbordone L, et al.. A clinical study of the outcomes and complications associated with maxillary sinus augmentation. Int J Oral Maxillofac Implants. 2006;21:81–85.
11. Becker ST, Terheyden H, Steinriede A, et al.. Prospective observation of 41 perforations of the Schneiderian membrane during sinus floor elevation. Clin Oral Implants Res. 2008;19:1285–1289.
12. Pikos MA. Maxillary sinus membrane repair: Update on technique for large and complete perforations. Implant Dent. 2008;17:24–31.
13. Testori T, Wallace SS, Del Fabbro M, et al.. Repair of large sinus membrane perforations using stabilized collagen barrier membranes: Surgical techniques with histologic and radiographic evidence of success. Int J Periodontics Restorative Dent. 2008;28:9–17.
14. Marx RE, Garg AK. A novel aid to elevation of the sinus membrane for the sinus lift procedure. Implant Dent. 2002;11:268–271.
15. Higgins TS, Hwang PH, Kingdom TT, et al.. Systematic review of topical vasoconstrictors in endoscopic sinus surgery. Laryngoscope. 2011;121:422–432.
16. Sarmento Junior KM, Tomita S, Kos AO. Topical use of adrenaline in different concentrations for endoscopic sinus surgery. Braz J Otorhinolaryngol. 2009;75:280–289.
17. Davenport RE, Porcelli RJ, Iacono VJ, et al.. Effects of anesthetics containing epinephrine
on catecholamine levels during periodontal surgery. J Periodontol. 1990;61:553–558.
18. Jastak JT, Yagiela JA. Vasoconstrictors and local anesthesia: A review and rationale for use. J Am Dent Assoc. 1983;107:623–630.
19. Tolas AG, Pflug AE, Halter JB. Arterial plasma epinephrine
concentrations and hemodynamic responses after dental injection of local anesthetic with epinephrine
. J Am Dent Assoc. 1982;104:41–43.
20. Nakamura Y, Matsumura K, Miura K, et al.. Cardiovascular and sympathetic responses to dental surgery with local anesthesia. Hypertens Res. 2001;24:209–214.
21. Silvestre FJ, Verdu MJ, Sanchis JM, et al.. Effects of vasoconstrictors in dentistry upon systolic and diastolic arterial pressure. Med Oral. 2001;6:57–63.
22. Fernieini EM, Bennett JD, Silverman DG, et al.. Hemodynamic assessment of local anesthetic administration by laser Doppler flowmetry. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;91:526–530.
23. Knoll-Kohler E, Knoller M, Brandt K, et al.. Cardiohemodynamic and serum catecholamine response to surgical removal of impacted mandibular third molars under local anesthesia: A randomized double-blind parallel group and crossover study. J Oral Maxillofac Surg. 1991;49:957–962.
24. Abraham-Inpijn L, Borgmeijer-Hoelen A, Gortzak RA. Changes in blood pressure
, heart rate
, and electrocardiogram during dental treatment with use of local anesthesia. J Am Dent Assoc. 1988;116:531–536.
25. Anderhuber W, Walch C, Nemeth E, et al.. Plasma adrenaline concentrations during functional endoscopic sinus surgery. Laryngoscope. 1999;109:204–207.
26. van Hasselt CA, Low JM, Waldron J, et al.. Plasma catecholamine levels following topical application versus infiltration of adrenaline for nasal surgery. Anaesth Intensive Care. 1992;20:332–336.
27. Rainer TH, Robertson CE. Adrenaline, cardiac arrest, and evidence based medicine. J Accid Emerg Med. 1996;13:234–237.
28. Kameyama K, Watanabe S, Kano T, et al.. Effects of nasal application of an epinephrine
and lidocaine mixture on the hemodynamics and nasal mucosa in oral and maxillofacial surgery. J Oral Maxillofac Surg. 2008;66:2226–2232.
29. Cassidy JP, Phero JC, Grau WH. Epinephrine
: Systemic effects and varying concentrations in local anesthesia. Anesth Prog. 1986;33:289–297.
30. Rosano G, Taschieri S, Gaudy JF, et al.. Maxillary sinus vascularization: A cadaveric study. J Craniofac Surg. 2009;20:940–943.
31. Dargaud J, Lamotte C, Dainotti JP, et al.. Venous drainage and innervation of the maxillary sinus [Article in French]. Morphologie. 2001;85:11–13.
32. Laragnoit AB, Neves RS, Neves IL, et al.. Locoregional anesthesia for dental treatment in cardiac patients: A comparative study of 2% plain lidocaine and 2% lidocaine with epinephrine
(1:100,000). Clinics (Sao Paulo). 2009;64:177–182.
33. Pikos MA. Maxillary sinus membrane repair: Report of a technique for large perforations. Implant Dent. 1999;8:29–34.
34. Ardekian L, Oved-Peleg E, Mactei EE, et al.. The clinical significance of sinus membrane perforation during augmentation of the maxillary sinus. J Oral Maxillofac Surg. 2006;64:277–282.
35. Oh E, Kraut RA. Effect of sinus membrane perforation on dental implant integration: A retrospective study on 128 patients. Implant Dent. 2011;20:13–19.
36. Garg AK. Augmentation grafting of the maxillary sinus for placement of dental implants: Anatomy, physiology, and procedures. Implant Dent. 1999;8:36–46.
37. Smiler DG. The sinus lift graft: Basic technique and variations. Pract Periodontics Aesthet Dent. 1997;9:885–893; quiz 95.
38. Perusse R, Goulet JP, Turcotte JY. Contraindications to vasoconstrictors in dentistry: Part I. Cardiovascular diseases. Oral Surg Oral Med Oral Pathol. 1992;74:679–686.