- Email: [email protected]
Clinical management of angioneurotic oedema patient post-orthognathic surgery
Int. J. Oral Maxillofac. Surg. 2011; 40: 106–123 available online at http://www.sciencedirect.com
Case Report Orthognathic Surgery
Clinical management of angioneurotic oedema patient post-orthognathic surgery
E. Puricelli, D. Ponzoni, F. E. Artuzi, G. L. Martins, T. Calcagnotto Oral and Maxillofacial Surgery, School of Dentistry, Federal University of Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos 2492, 90035-003, Porto Alegre, RS, Brazil
E. Puricelli, D. Ponzoni, F. E. Artuzi, G. L. Martins, T. Calcagnotto: Clinical management of angioneurotic oedema patient post-orthognathic surgery. Int. J. Oral Maxillofac. Surg. 2011; 40: 106–123. # 2010 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Abstract. Angioneurotic oedema is an acute swelling involving the submucosal or subcutaneous tissues; it is most often located in the oral and maxillofacial region, which can result in upper airway obstruction. Its aetiology is frequently associated with immunoglobulin-mediated hypersensitivity reactions that elicit a heightened inflammatory response. The objective of this study was to report the case of a patient who developed an episode of angioneurotic oedema following combined orthognathic surgery. Pharmacological and nonpharmacological interventions used in the treatment of this important clinical condition are described and discussed.
Introduction
In 1876, Milton clinically described the occurrence of a ‘giant urticaria’, naming it angioedema5. This condition is characterized by diffuse swelling, and the most commonly affected areas are the face, tongue, pharynx, and larynx, which can lead to upper airway obstruction7. In the acquired form of angioneurotic oedema, which is idiopathic and closely resembles classic allergic reactions, the therapeutic use of epinephrine and steroid supplements, such as hydrocortisone, is associated with a good response to treatment7. In cases with a history of oedema, usually involving C1 inhibitor (C1-INH) deficiency, prophylactic therapy is recommended3. Postoperative oedema is expected after oral and maxillofacial surgery, which can affect the tongue and pharyngeal region, resulting in upper airway obstruction. If the angioneurotic oedema is associated 0901-5027/010106 + 018 $36.00/0
with clinical conditions, respiratory function may be compromised1,3,4,7. Considering the seriousness of this condition, immediate diagnosis and treatment is of paramount importance to avoid life-threatening complications.
Case report
A 21-year-old white woman, weighing 58 kg, with no history of systemic alterations or allergies, presented with oral and maxillofacial asymmetry, characterized by mandibular retrusion and right-sided deviation. She had a left unilateral cleft lip and palate that had been treated previously. Owing to maxillomandibular discrepancy, the patient underwent orthognathic treatment. During surgery, a mandibular sagittal split ramus osteotomy (Puricelli osteotomy)6 was performed on the left side; a mandibular vertical ramus osteotomy on
Accepted for publication 6 April 2010 Available online 19 August 2010
the right side; and a maxillary alveolar segmental osteotomy on the right side. After surgery, the patient was transferred to the recovery room and remained intubated and sedated, receiving analgesic (fentanyl), antiemetic (ondansetron hydrochloride) and antipyretic (dipyrone) medication, according to prescription. Extra care, such as the application of heat/cold modalities, was also performed as a routine procedure to help reduce postoperative oedema. Immediately after surgery, visible facial swelling was consistent with the procedure performed. The enhanced swelling observed in the lips and periorbital region, in both sides, during the postoperative period led to a clinical diagnosis of angioneurotic oedema (Fig. 1). The patient was then administered hydrocortisone (100 mg i.v. at 8-h intervals) and epinephrine (3 mg diluted in 3 ml saline solution, via nasal
# 2010 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Management of postoperative angioedema
107
Fig. 1. Heightened inflammatory reaction in the lips and periorbital region, in both sides (surgeons/authors: EP and DP).
nebulization, at 12-h intervals). About 7 h after the patient was started on hydrocortisone, the oedema was intense, but with initial signs of reduction. 2 days after surgery, the established therapeutic management significantly reduced the oedema. Hydrocortisone and epinephrine administration was continued, and the administration of anti-inflammatory drugs was started (tenoxicam, 20 mg i.v. once a day). This drug regimen reduced the angioneurotic oedema, unblocking airways and allowing safe extubation of the patient on the third day. 5 days after surgery, the patient was discharged with reduced facial oedema consistent with the postoperative status of the procedure performed (Fig. 2). Figure 3 shows the patient 16 months after surgery. Discussion
In the postoperative period following surgical procedures, such as combined orthognathic surgery, facial swelling is
expected2. If this sign progressively becomes worse and pathological, as in the case reported here, it is called angioneurotic oedema (or angioedema). Angioedema may be inherited (hereditary angioedema) or acquired (acquired angioedema), and both forms share similar clinical features: intense facial swelling, especially in the lips and tongue, also involving the eyelids and chin. This condition evolves suddenly, but also shows rapid regression, and may involve the abdominal region and extremities, mainly in the hereditary form. Hereditary angioedema is always associated with C1-INH deficiency, as well as a family history of angioedema. When angioedema is related to this protein, lymphoproliferative disorders or autoantibodies to C1-INH are also present5,7. In the acquired form, most cases are of idiopathic origin3. C1-INH is a glucoprotein of the serine protease inhibitor (serpin) family involved in the coagulation cascade, fibrinolysis and the kallikrein-quinine system, thus inacti-
vating plasmin, kallikrein and Hageman factor (factor XII). Deficiency of C1-INH leads to increased vascular permeability, resulting in angioneurotic oedema3,4. The patient in the present case had no systemic alterations or family history of angioedema, and developed the acquired form of the disease after surgery. In addition, C1-INH and C4 plasma levels were normal (Table 1), contrasting with the hereditary form, which may exhibit reduced plasma levels of these components5. It is important to highlight that the main clinical manifestations of this condition are located on the face, so oral health care providers, particularly oral and maxillofacial surgeons, should be able to identify its signs and symptoms, thus establishing differential diagnoses. The pathogenesis of acquired angioedema involves, mainly, antigen- and immunoglobulin (Ig)E-induced histamine release, as in anaphylactic reactions. Other chemical mediators released include vasoactive proteins, such as histamine, bra-
108
Puricelli et al.
Fig. 2. Regression of facial angioneurotic oedema. Remaining oedema consistent with the postoperative status of the orthognathic surgery performed.
dykinin, prostaglandin D, leukotrienes C and D, and platelet-activating factors. These substances, which mediate inflammatory response, cause positive feedback for the development of pathologic oedema7. Angioedema lesions are painless and do not show high temperature. Acquired angioneurotic oedema, with no C1-INH involvement, is often interpreted as an allergic reaction3, because it presents itching symptoms similar to urticaria. This characteristic is not observed in hereditary angioedema2. Lesions are fluid filled or slightly firm. Volume increase is regular and diffuse3. The enhanced oedema involving the lips and periorbital region oriented diagnosis in the present case. When treated appropriately, the acute condition is controlled, improving within a few hours up to 3 days3,4. The patient, who underwent combined orthognathic surgery, showed regression of the angioedema in about 2 days after the procedure; an improvement in the postoperative oedema that was consistent with the surgical procedure performed (Fig. 2).
Angioneurotic oedema can be treated by corticosteroid administration, but the use of hydrocortisone alone is not effective during the acute phase, due to its long period of latency9. In this patient, the use of hydrocortisone was associated with nebulized epinephrine, which allowed a faster clinical effect on oedema regression4. When the medication is inhaled in relatively concentrated solutions, actions are restricted to the respiratory tract, thus in the case of angioedema, airways are kept clear10. In addition to corticosteroids, antihistamines are also indicated in the treatment of angioneurotic oedema, since the non-hereditary form of this condition may be an allergic reaction3. H1-receptor antagonists are more useful in acute allergic cases. They strongly block the increase in capillary permeability and the formation of histamine-induced swelling and urticarial plaques. In angioedema in which autacoids other than histamine also play important roles, epinephrine is the core of treatment. Histamine antagonists play only a secondary and adjuvant role8.
In cases of acute angioedema, related to protein deficiency, the administration of fresh frozen plasma and C1-INH concentrate is effective in reducing the oedema2. In chronic situations, long-term prophylactic therapy is often based on the use of androgens such as danazol and stanozolol2,7. Antifibrinolytic agents, such as eaminocaproic acid, are also effective and can be used in continuous prophylaxis2. In the present patient, the absence of systemic alterations and adverse events in previous dental procedures indicated no need for corticosteroid prophylaxis. Corticosteroid administration is indicated in cases of hereditary angiooedema or cases related to previous manifestations of the disease. In acute manifestations, with a risk of airway obstruction, immediate intubation and epinephrine administration are indicated5. In severe cases, intubation may be difficult, leading to the indication for tracheostomy1. In the present case, due to a severe and acute condition, the postoperative intubation period was prolonged as a
Management of postoperative angioedema
109
Funding
None. Competing interests
None declared. Ethical approval
Not required. References
Fig. 3. Postoperative aspect after 16 months.
Table 1. Quantification of C1-INH and C4 levels. Complement components
Complement fraction* (mg/dl)
C1-INH C4
22.9 14.5
Reference values (mg/dl) 15–34 10–40
C1-INH = C1 inhibitor. * Plasma concentration during the absence of angioedema.
complementary measure to clinical and pharmacological treatment. Drawing a relationship between angioneurotic oedema and the surgical procedure performed, the authors focus attention on three aspects of the process. First, a detailed analysis of factors from the patient’s history is of utmost importance, since angioedema may be related to family history or previous dental proce-
dures. Second, the appropriate surgical technique and the surgeon’s professional knowledge and competence are decisive factors in minimizing the probability of angioneurotic oedema occurrence. Third, the importance of the postoperative period is emphasized, during which some therapeutic measures, whether pharmacological or not, should be employed to inhibit excessive swelling.
1. Atkinson JC, Frank MM. Oral manifestations and dental management of patients with hereditary angioedema. J Oral Pathol Med 1991: 20: 139–142. 2. Bork K, Barnstedt SE. Laryngeal edema and death from asphyxiation after tooth extraction in four patients with hereditary angioedema. J Am Dent Assoc 2003: 134: 1088–1094. 3. Correll RW, DeBoom GW, Jensen JL. Rapidly developing, edematous swelling of the upper lip. J Am Dent Assoc 1986: 113: 69–70. 4. Degroote DF, Smith GL, Huttula GS. Acute airway obstruction following tooth extraction in hereditary angioedema. J Oral Maxillofac Surg 1985: 43: 52–54. 5. Lin JH, Casillas AM, Sattar S. C1esterase inhibitor autoantibodies in a patient with acute tongue swelling. Allergy Asthma Proc 2007: 28: 93–96. 6. Puricelli E. A new technique for mandibular osteotomy. Head Face Med 2007: 3: 15. 7. Rees SR, Gibson J. Angioedema and swellings of the orofacial region. Oral Dis 1997: 3: 39–42. 8. Skidgel RA, Erdo¨s EG. Histamine, bradykinin and their antagonists. In: Brunton LL, Lazo JS, Parker KL, eds: Goodman & Gilman’s the Pharmacological Basis of Therapeutics. New York: McGraw-Hill Companies 2006: 629–651. 9. Wannmacher L, Ferreira MBC. Farmacologia Clı´nica Para Dentistas. Antiinflamato´rios Estero´ides. Rio de Janeiro: Guanabara Koogan 2007: pp. 261–269. 10. Westfall TC, Westfall DP. Adrenergic agonists and antagonists. In: Brunton LL, Lazo JS, Parker KL, eds: Goodman & Gilman’s the Pharmacological Basis of Therapeutics. New York: McGraw-Hill Companies 2006: 237–296. Address: Thiago Calcagnotto School of Dentistry UFRGS Rua Ramiro Barcelos 2492 90035-003 Porto Alegre RS Brazil Tel.: +55 51 3308 5399 fax: +55 51 3308 5399 E-mail: [email protected] doi:10.1016/j.ijom.2010.04.055
Case Report Orthognathic Surgery
Clinical management of angioneurotic oedema patient post-orthognathic surgery
E. Puricelli, D. Ponzoni, F. E. Artuzi, G. L. Martins, T. Calcagnotto Oral and Maxillofacial Surgery, School of Dentistry, Federal University of Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos 2492, 90035-003, Porto Alegre, RS, Brazil
E. Puricelli, D. Ponzoni, F. E. Artuzi, G. L. Martins, T. Calcagnotto: Clinical management of angioneurotic oedema patient post-orthognathic surgery. Int. J. Oral Maxillofac. Surg. 2011; 40: 106–123. # 2010 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Abstract. Angioneurotic oedema is an acute swelling involving the submucosal or subcutaneous tissues; it is most often located in the oral and maxillofacial region, which can result in upper airway obstruction. Its aetiology is frequently associated with immunoglobulin-mediated hypersensitivity reactions that elicit a heightened inflammatory response. The objective of this study was to report the case of a patient who developed an episode of angioneurotic oedema following combined orthognathic surgery. Pharmacological and nonpharmacological interventions used in the treatment of this important clinical condition are described and discussed.
Introduction
In 1876, Milton clinically described the occurrence of a ‘giant urticaria’, naming it angioedema5. This condition is characterized by diffuse swelling, and the most commonly affected areas are the face, tongue, pharynx, and larynx, which can lead to upper airway obstruction7. In the acquired form of angioneurotic oedema, which is idiopathic and closely resembles classic allergic reactions, the therapeutic use of epinephrine and steroid supplements, such as hydrocortisone, is associated with a good response to treatment7. In cases with a history of oedema, usually involving C1 inhibitor (C1-INH) deficiency, prophylactic therapy is recommended3. Postoperative oedema is expected after oral and maxillofacial surgery, which can affect the tongue and pharyngeal region, resulting in upper airway obstruction. If the angioneurotic oedema is associated 0901-5027/010106 + 018 $36.00/0
with clinical conditions, respiratory function may be compromised1,3,4,7. Considering the seriousness of this condition, immediate diagnosis and treatment is of paramount importance to avoid life-threatening complications.
Case report
A 21-year-old white woman, weighing 58 kg, with no history of systemic alterations or allergies, presented with oral and maxillofacial asymmetry, characterized by mandibular retrusion and right-sided deviation. She had a left unilateral cleft lip and palate that had been treated previously. Owing to maxillomandibular discrepancy, the patient underwent orthognathic treatment. During surgery, a mandibular sagittal split ramus osteotomy (Puricelli osteotomy)6 was performed on the left side; a mandibular vertical ramus osteotomy on
Accepted for publication 6 April 2010 Available online 19 August 2010
the right side; and a maxillary alveolar segmental osteotomy on the right side. After surgery, the patient was transferred to the recovery room and remained intubated and sedated, receiving analgesic (fentanyl), antiemetic (ondansetron hydrochloride) and antipyretic (dipyrone) medication, according to prescription. Extra care, such as the application of heat/cold modalities, was also performed as a routine procedure to help reduce postoperative oedema. Immediately after surgery, visible facial swelling was consistent with the procedure performed. The enhanced swelling observed in the lips and periorbital region, in both sides, during the postoperative period led to a clinical diagnosis of angioneurotic oedema (Fig. 1). The patient was then administered hydrocortisone (100 mg i.v. at 8-h intervals) and epinephrine (3 mg diluted in 3 ml saline solution, via nasal
# 2010 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Management of postoperative angioedema
107
Fig. 1. Heightened inflammatory reaction in the lips and periorbital region, in both sides (surgeons/authors: EP and DP).
nebulization, at 12-h intervals). About 7 h after the patient was started on hydrocortisone, the oedema was intense, but with initial signs of reduction. 2 days after surgery, the established therapeutic management significantly reduced the oedema. Hydrocortisone and epinephrine administration was continued, and the administration of anti-inflammatory drugs was started (tenoxicam, 20 mg i.v. once a day). This drug regimen reduced the angioneurotic oedema, unblocking airways and allowing safe extubation of the patient on the third day. 5 days after surgery, the patient was discharged with reduced facial oedema consistent with the postoperative status of the procedure performed (Fig. 2). Figure 3 shows the patient 16 months after surgery. Discussion
In the postoperative period following surgical procedures, such as combined orthognathic surgery, facial swelling is
expected2. If this sign progressively becomes worse and pathological, as in the case reported here, it is called angioneurotic oedema (or angioedema). Angioedema may be inherited (hereditary angioedema) or acquired (acquired angioedema), and both forms share similar clinical features: intense facial swelling, especially in the lips and tongue, also involving the eyelids and chin. This condition evolves suddenly, but also shows rapid regression, and may involve the abdominal region and extremities, mainly in the hereditary form. Hereditary angioedema is always associated with C1-INH deficiency, as well as a family history of angioedema. When angioedema is related to this protein, lymphoproliferative disorders or autoantibodies to C1-INH are also present5,7. In the acquired form, most cases are of idiopathic origin3. C1-INH is a glucoprotein of the serine protease inhibitor (serpin) family involved in the coagulation cascade, fibrinolysis and the kallikrein-quinine system, thus inacti-
vating plasmin, kallikrein and Hageman factor (factor XII). Deficiency of C1-INH leads to increased vascular permeability, resulting in angioneurotic oedema3,4. The patient in the present case had no systemic alterations or family history of angioedema, and developed the acquired form of the disease after surgery. In addition, C1-INH and C4 plasma levels were normal (Table 1), contrasting with the hereditary form, which may exhibit reduced plasma levels of these components5. It is important to highlight that the main clinical manifestations of this condition are located on the face, so oral health care providers, particularly oral and maxillofacial surgeons, should be able to identify its signs and symptoms, thus establishing differential diagnoses. The pathogenesis of acquired angioedema involves, mainly, antigen- and immunoglobulin (Ig)E-induced histamine release, as in anaphylactic reactions. Other chemical mediators released include vasoactive proteins, such as histamine, bra-
108
Puricelli et al.
Fig. 2. Regression of facial angioneurotic oedema. Remaining oedema consistent with the postoperative status of the orthognathic surgery performed.
dykinin, prostaglandin D, leukotrienes C and D, and platelet-activating factors. These substances, which mediate inflammatory response, cause positive feedback for the development of pathologic oedema7. Angioedema lesions are painless and do not show high temperature. Acquired angioneurotic oedema, with no C1-INH involvement, is often interpreted as an allergic reaction3, because it presents itching symptoms similar to urticaria. This characteristic is not observed in hereditary angioedema2. Lesions are fluid filled or slightly firm. Volume increase is regular and diffuse3. The enhanced oedema involving the lips and periorbital region oriented diagnosis in the present case. When treated appropriately, the acute condition is controlled, improving within a few hours up to 3 days3,4. The patient, who underwent combined orthognathic surgery, showed regression of the angioedema in about 2 days after the procedure; an improvement in the postoperative oedema that was consistent with the surgical procedure performed (Fig. 2).
Angioneurotic oedema can be treated by corticosteroid administration, but the use of hydrocortisone alone is not effective during the acute phase, due to its long period of latency9. In this patient, the use of hydrocortisone was associated with nebulized epinephrine, which allowed a faster clinical effect on oedema regression4. When the medication is inhaled in relatively concentrated solutions, actions are restricted to the respiratory tract, thus in the case of angioedema, airways are kept clear10. In addition to corticosteroids, antihistamines are also indicated in the treatment of angioneurotic oedema, since the non-hereditary form of this condition may be an allergic reaction3. H1-receptor antagonists are more useful in acute allergic cases. They strongly block the increase in capillary permeability and the formation of histamine-induced swelling and urticarial plaques. In angioedema in which autacoids other than histamine also play important roles, epinephrine is the core of treatment. Histamine antagonists play only a secondary and adjuvant role8.
In cases of acute angioedema, related to protein deficiency, the administration of fresh frozen plasma and C1-INH concentrate is effective in reducing the oedema2. In chronic situations, long-term prophylactic therapy is often based on the use of androgens such as danazol and stanozolol2,7. Antifibrinolytic agents, such as eaminocaproic acid, are also effective and can be used in continuous prophylaxis2. In the present patient, the absence of systemic alterations and adverse events in previous dental procedures indicated no need for corticosteroid prophylaxis. Corticosteroid administration is indicated in cases of hereditary angiooedema or cases related to previous manifestations of the disease. In acute manifestations, with a risk of airway obstruction, immediate intubation and epinephrine administration are indicated5. In severe cases, intubation may be difficult, leading to the indication for tracheostomy1. In the present case, due to a severe and acute condition, the postoperative intubation period was prolonged as a
Management of postoperative angioedema
109
Funding
None. Competing interests
None declared. Ethical approval
Not required. References
Fig. 3. Postoperative aspect after 16 months.
Table 1. Quantification of C1-INH and C4 levels. Complement components
Complement fraction* (mg/dl)
C1-INH C4
22.9 14.5
Reference values (mg/dl) 15–34 10–40
C1-INH = C1 inhibitor. * Plasma concentration during the absence of angioedema.
complementary measure to clinical and pharmacological treatment. Drawing a relationship between angioneurotic oedema and the surgical procedure performed, the authors focus attention on three aspects of the process. First, a detailed analysis of factors from the patient’s history is of utmost importance, since angioedema may be related to family history or previous dental proce-
dures. Second, the appropriate surgical technique and the surgeon’s professional knowledge and competence are decisive factors in minimizing the probability of angioneurotic oedema occurrence. Third, the importance of the postoperative period is emphasized, during which some therapeutic measures, whether pharmacological or not, should be employed to inhibit excessive swelling.
1. Atkinson JC, Frank MM. Oral manifestations and dental management of patients with hereditary angioedema. J Oral Pathol Med 1991: 20: 139–142. 2. Bork K, Barnstedt SE. Laryngeal edema and death from asphyxiation after tooth extraction in four patients with hereditary angioedema. J Am Dent Assoc 2003: 134: 1088–1094. 3. Correll RW, DeBoom GW, Jensen JL. Rapidly developing, edematous swelling of the upper lip. J Am Dent Assoc 1986: 113: 69–70. 4. Degroote DF, Smith GL, Huttula GS. Acute airway obstruction following tooth extraction in hereditary angioedema. J Oral Maxillofac Surg 1985: 43: 52–54. 5. Lin JH, Casillas AM, Sattar S. C1esterase inhibitor autoantibodies in a patient with acute tongue swelling. Allergy Asthma Proc 2007: 28: 93–96. 6. Puricelli E. A new technique for mandibular osteotomy. Head Face Med 2007: 3: 15. 7. Rees SR, Gibson J. Angioedema and swellings of the orofacial region. Oral Dis 1997: 3: 39–42. 8. Skidgel RA, Erdo¨s EG. Histamine, bradykinin and their antagonists. In: Brunton LL, Lazo JS, Parker KL, eds: Goodman & Gilman’s the Pharmacological Basis of Therapeutics. New York: McGraw-Hill Companies 2006: 629–651. 9. Wannmacher L, Ferreira MBC. Farmacologia Clı´nica Para Dentistas. Antiinflamato´rios Estero´ides. Rio de Janeiro: Guanabara Koogan 2007: pp. 261–269. 10. Westfall TC, Westfall DP. Adrenergic agonists and antagonists. In: Brunton LL, Lazo JS, Parker KL, eds: Goodman & Gilman’s the Pharmacological Basis of Therapeutics. New York: McGraw-Hill Companies 2006: 237–296. Address: Thiago Calcagnotto School of Dentistry UFRGS Rua Ramiro Barcelos 2492 90035-003 Porto Alegre RS Brazil Tel.: +55 51 3308 5399 fax: +55 51 3308 5399 E-mail: [email protected] doi:10.1016/j.ijom.2010.04.055